Apparatus and method for setting the parameters of an alert window used for timing the delivery of ETC signals to a heart under varying cardiac conditions

ABSTRACT

A method for setting the parameters of an alert time window in an excitable tissue control device operative under a plurality of different cardiac conditions of a heart of a patient. The method includes providing said excitable tissue control device with a set of data including a plurality of sets of alert time window parameters. Each set of window parameters is uniquely associated with a different set of values of a plurality of cardiac condition defining parameters identifying one of the different cardiac conditions. Each set of window parameters includes at least a set of timing parameters usable for obtaining a beginning time point and an ending time point of the alert window. The sets of window parameters are obtained by processing data collected within a data collection session from a plurality of cardiac beats of the same patient under the different cardiac conditions. The methods updates for each current beat cycle the values of a plurality of cardiac condition defining variables corresponding to said cardiac condition defining parameters, automatically selects a current set of alert time window parameters based on the current values of the cardiac condition defining variables, starts and terminates the alert time window based on the time of detecting a first depolarization event at a first cardiac site, detects within the duration of the alert window a second depolarization event at a second cardiac site, and triggers the delivery of a delayed non-excitatory excitable tissue control signal at the second cardiac site based on the time of detection of the second depolarization event. The different cardiac conditions include different beat cycle lengths, and may include beats which are or are not influenced by prior application of ETC signals to the heart and, where relevant, naturally and artificially paced beats. The alert window parameters may include an event detection sensitivity level parameter. Implantable and external devices are describe which are adapted for implementing the disclosed method.

RELATED U.S. PATENT APPLICATIONS

This Application is a continuation in part of U.S. patent applicationSer. No. 09/328,068, to Mika et al., titled “APPARATUS AND METHOD FORCOLLECTING DATA USEFUL FOR DETERMINING THE PARAMETERS OF AN ALERT WINDOWFOR TIMING DELIVERY OF ETC SIGNALS TO A HEART UNDER VARYING CARDIACCONDITIONS”, filed Jun. 8, 1999, the entire specification of which isincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to the field of methods andmedical devices for modulating cardiac muscle activity and contractilityand more specifically to methods and devices for setting the parametersof a detection time window used for initiating the delivery of excitabletissue controller (ETC) signals under a variety of conditions includingvarying heart rates, paced or sensed beats and the absence and presenceof ETC signals' effects on the velocity of propagation of a cardiacdepolarization wave.

BACKGROUND OF THE INVENTION

Excitable tissue controllers (ETCs) are devices which modulate theactivity of excitable tissues by application of non-excitatoryelectrical stimulation to the excitable tissue through suitableelectrodes in contact with the tissue. For example, ETC devices may beused, inter alia, to increase or decrease the contractility of cardiacmuscle in vitro, in vivo and in situ., as disclosed in detail in PCTapplication, International Publication Number WO 97/25098 to Ben-Haim etal., titled “ELECTRICAL MUSCLE CONTROLLER”, incorporated herein byreference. Other methods and applications of ETC devices are disclosedin PCT applications commonly-assigned to the assignee of the presentapplication, International Publication Number WO 98/10828, titled“APPARATUS AND METHOD FOR CONTROLLING THE CONTRACTILITY OF MUSCLES” toBen Haim et al., incorporated herein by reference, InternationalPublication Number WO 98/10829, titled “DRUG-DEVICE COMBINATION FORCONTROLLING THE CONTRACTILITY OF MUSCLES” to Ben Haim et al.,incorporated herein by reference and International Publication Number WO98/10830, titled “FENCING OF CARDIAC MUSCLES” to Ben Haim et al.,incorporated herein by reference, International Publications Number WO98/10831 to Ben Haim et al., titled “CARDIAC OUTPUT CONTROLLER”,incorporated herein by reference.

Further applications of the ETC including devices combining cardiacpacing and cardiac contractility modulation are disclosed in PCTApplication, International Publication No. WO 98/10832, titled “CARDIACOUTPUT ENHANCED PACEMAKER” to Ben Haim et al., co-assigned to theassignee of the present application. Such ETC devices function byapplying non-excitatory electrical field signals of suitable amplitudeand waveform, appropriately timed with respect to the heart's intrinsicelectrical activity to selected cardiac segments. The contraction of theselected segments can be modulated to increase or decrease the strokevolume of the heart. The timing of the ETC signals must be carefullycontrolled since application of the ETC signal to the myocardium atinappropriate times may be arrhythmogenic. The ETC signals musttherefore be applied to the selected cardiac segment within a definedtime interval during which the selected cardiac segment will not bestimulated by the ETC signals.

As disclosed in International Publication No. WO 98/10832, the ETCsignals may be timed relative to a trigger signal which is also used asa pacing trigger, or may be timed relative to locally sensed electrogramsignals.

U.S. patent application to Mika et al., Ser. No. 09/276,460, Titled“APPARATUS AND METHOD FOR TIMING THE DELIVERY OF NON-EXCITATORY ETCSIGNALS TO A HEART”, filed Mar. 25, 1999 and assigned to the commonassignee of the present application, the entire specification of whichis incorporated herein by reference, discloses a method for timing thedelivery of non-excitatory ETC signals to a heart using, inter alia, analert window period for reducing the probability of delivering animproperly timed ETC signal to the heart due to spurious detection ofnoise or ectopic beats.

The methods of timing of the delivery of ETC signals disclosedhereinabove do not take into account the fact that naturally occurringand pacemaker induced changes in heart rate (HR) may cause changes inthe velocity of propagation of the depolarization wave in themyocardium. Additionally, the delivery of the ETC signals to themyocardium may also cause changes in the velocity of propagation of thedepolarization wave in the myocardium. Other factors such as, interalia, various cardio-active drug treatments and myocardial pathologicalconditions such as ischemia may also cause changes in the velocity ofpropagation of the depolarization wave in the myocardium. It istherefore desirable to have a method for determining proper timing ofthe delivery of ETC signals which takes into account variations invelocity of propagation of the depolarization wave in the myocardiumunder different cardiac conditions.

SUMMARY OF THE INVENTION

There is therefore provided, in accordance with a preferred embodimentof the present invention, a method for setting the parameters of analert time window in an excitable tissue control device operative undera plurality of different cardiac conditions of a heart of a patient. Themethod includes the step of providing the excitable tissue controldevice with a set of data. The set of data includes a plurality of setsof alert time window parameters. Each set of alert time windowparameters is associated with one of the plurality of different cardiacconditions. Each set of alert time window parameters includes at least aset of timing parameters usable for obtaining a beginning time point andan ending time point for the alert time window. Each set of theplurality of sets of alert time window parameters is obtained byprocessing data collected from a plurality of cardiac beats of the heartof the patient under the plurality of different cardiac conditionswithin a data collection session prior to the step of providing. Themethod further includes the step of automatically selecting, for acurrent beat cycle of the heart, a current set of alert time windowparameters of the plurality of sets of alert time window parametersbased on the current cardiac conditions detected for the current beatcycle. The method further includes the step of using, for the currentbeat cycle, the current set of alert time window parameters selected inthe step of automatically selecting to start and terminate the alerttime window based on the time of detecting a first depolarization eventat or about a first cardiac site. The method further includes the stepsof detecting, within the duration of the alert time window of thecurrent beat cycle, a second depolarization event at a second cardiacsite of the heart, and triggering the delivery of a delayednon-excitatory excitable tissue control signal at or about the secondcardiac site based on the time of detection of the second depolarizationevent.

There is further provided, in accordance with a preferred embodiment ofthe present invention, a method for setting the parameters of an alerttime window in an excitable tissue control device operative under aplurality of different cardiac conditions of a heart of a patient. Themethod includes the step of providing the excitable tissue controldevice with a set of data. The set of data includes a plurality of setsof alert time window parameters. Each set of alert time windowparameters is uniquely associated with a different set of values of aplurality of cardiac condition defining parameters identifying one ofthe plurality of different cardiac conditions. Each set of alert timewindow parameters of the plurality of sets of alert time windowparameters includes at least a set of timing parameters usable forobtaining a beginning time point and an ending time point for the alerttime window. Each set of alert time window parameters is obtained byprocessing data collected from a plurality of cardiac beats of the heartof the patient under the plurality of different cardiac conditionswithin a data collection session prior to the step of providing. Themethod further includes the step of updating for a current beat cycle ofthe heart the values of a plurality of cardiac condition definingvariables corresponding to the cardiac condition defining parameters.The method further includes the step of automatically selecting for thecurrent beat cycle a current set of alert time window parameters of theplurality of sets of alert time window parameters based on the currentvalues of the cardiac condition defining variables. The method furtherincludes the step of using, for the current beat cycle, the current setof alert time window parameters selected in the step of automaticallyselecting to start and terminate the alert time window based on the timeof detecting a first depolarization event at or about a first cardiacsite. The method further includes the steps of detecting within theduration of the alert time window of the current beat cycle a seconddepolarization event at a second cardiac site of the heart, andtriggering the delivery of a delayed non-excitatory excitable tissuecontrol signal at or about the second cardiac site based on the time ofdetection of the second depolarization event.

There is also provided, in accordance with a preferred embodiment of thepresent invention, an excitable tissue control device for setting, on abeat by beat basis, the parameters of an alert time window under aplurality of different cardiac conditions of a heart of a patient. Thedevice includes a plurality of electrodes implanted in or about theheart. The device further includes detection circuitry for detectingelectrical depolarization events in a first cardiac site through atleast a first electrode of the plurality of electrodes. The firstelectrode is disposed in or about the first cardiac site. The detectioncircuitry is also used for detecting electrical depolarization events ina second cardiac site through at least a second electrode of theplurality of electrodes. The second electrode is disposed in or aboutthe second cardiac site. The device further includesan excitable tissuecontrol unit for delivering non-excitatory excitable tissue controlsignals to at least part of the second cardiac site through one or moreelectrodes of the plurality of electrodes. The device further includes amemory unit for storing a set of data. The set of data includes aplurality of sets of alert time window parameters. Each set of alerttime window parameters is uniquely associated with a different set ofvalues of a plurality of cardiac condition defining parametersidentifying one of the plurality of different cardiac conditions. Eachset of alert time window parameters includes at least a set of timingparameters usable for obtaining a beginning time point and an endingtime point for the alert time window. Each set of alert time windowparameters is obtained by processing data collected from a plurality ofcardiac beats of the heart of the patient under the plurality ofdifferent cardiac conditions within a data collection session performedin the patient. The device further includes a processor unit operativelyconnected to the detection circuitry, the excitable tissue control unitand the memory unit. The processor unit is usable for receivingdetection signals from the detection circuitry, for controlling theexcitable tissue control unit by using the received detection signals,for updating in a current beat cycle of the heart the values of aplurality of cardiac condition defining variables corresponding to thecardiac condition defining parameters, for automatically selecting forthe current beat cycle a current set of alert time window parameters ofthe plurality of sets of alert time window parameters based on thecurrent values of the cardiac condition defining variables, for applyingthe current set of alert time window parameters to start the alert timewindow within the current beat cycle after detecting a firstdepolarization event at or about the first cardiac site and to terminatethe alert time window, and for initiating the delivery of a delayedexcitable tissue control signal at or about the second cardiac site upondetecting, within the duration of the alert time window, adepolarization event in or about the second cardiac site of the heart.The device further includes a power source for providing power to thedetection circuitry, the processor unit the memory unit and theexcitable tissue control unit.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the device further includes a telemetry unitoperatively connected to the power source and the processor unit fortelemetrically receiving data from a second telemetry unit disposedoutside the patient.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the plurality of sets of alert time window parametersof the set of data are stored in the memory unit as a data array or alook up table.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the detection circuitry is adapted for beingcontrollably switched between a plurality of detection sensitivitylevels, and each set of alert time window parameters of the plurality ofsets of alert time window parameters further includes at least onedetection sensitivity parameter having a value representing one of theplurality of detection sensitivity levels of the detection circuitry,and the processor unit is adapted for using the value of the at leastone detection sensitivity parameter of the current beat cycle to switchthe detection circuitry to a detection sensitivity level represented bythe at least one detection sensitivity parameter of the current beatcycle.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the detection circuitry is adapted for being switchedbetween a plurality of voltage threshold levels and the at least onedetection sensitivity parameter includes a voltage threshold level.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the detection circuitry is adapted for performingevent detection based on a morphological detection method and whereinthe at least one detection sensitivity parameter includes at least onemorphological detection parameter.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the set of data is a degenerate set of data in whichat least some of the sets of alert time window parameters of theplurality of sets of alert time window parameters have identical valuesof the at least one detection sensitivity parameter.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the plurality of cardiac conditions includes beatshaving a plurality of different beat to beat time intervals representingdifferent instantaneous heart rates of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the plurality of cardiac conditions further includesbeats occurring during a time period in which the prior application ofexcitable tissue control signals results in a change of the velocity ofpropagation of a depolarization wave in at least a portion of themyocardial tissue disposed between the first cardiac site and the secondcardiac site of the heart, and beats occurring during a time period inwhich the prior application of excitable tissue control signals does notresult in a change in the velocity of propagation of a depolarizationwave in at least a portion of the myocardial tissue disposed between thefirst cardiac site and the second cardiac site of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the device further includes a pacing unit operativelyconnected to the power source, the processor unit and to at least oneelectrode of the plurality of electrodes, for delivering pacing pulsesto the heart through the at least one electrode.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the plurality of cardiac conditions includes beatsinitiated by the natural pacemaker of the heart and beats initiated by apacing pulse delivered by the excitable tissue control device.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the set of timing parameters of the alert time windowparameters includes a beginning time point value and an ending timepoint value for the alert time window.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the excitable tissue control device is provided witha value of the bin duration of a time bin used for collecting datawithin the data collection session. The value is stored in the memoryunit. The set of timing parameters of the alert time window parametersincludes a starting bin number and an ending bin number, and theprocessor unit is adapted for computing the starting time point andending time point of the alert time window from the bin duration, thestarting bin number and the ending bin number, prior to starting of thealert time window within the current beat cycle.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the set of timing parameters includes a set ofapproximation parameters and wherein the processing of the datacollected from the heart in the data collection session includes usingan approximation method to obtain a plurality of sets of approximationparameters usable for computing improved approximated values of thebeginning time point and the ending time point of the alert time window.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the approximation method is a linear piecewiseapproximation method. The set of approximation parameters includes abeginning time point parameter and a first slope parameter associatedwith the beginning time point parameter. The set of approximationparameters also includes an ending time point parameter and a secondslope parameter associated with the ending time point parameter. Thestep of using includes computing an approximated beginning time pointfor the alert time window of the current beat cycle from the values ofthe current cycle length measured for the current beat cycle, the firstslope parameter and the beginning time point parameter, and computing anapproximated ending time point for the alert time window of the currentbeat cycle from the values of the current cycle length, the second slopeparameter and the ending time point parameter.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the current cycle length is the instantaneous cyclelength determined from the current R—R interval or the current A—Ainterval measured for the current beat cycle.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the current cycle length is an average cycle lengthcomputed from the values of a plurality of consecutive R—R intervalsincluding the R—R interval of the current beat cycle.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the current cycle length is an average cycle lengthcomputed from the values of a plurality of consecutive A—A intervalsincluding the A—A interval of the current beat cycle.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the set of data is a degenerate set of data in whichat least some of the sets of alert time window parameters of theplurality of sets of alert time window parameters have identical valuesof the set of timing parameters.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the first cardiac site is the right ventricle of theheart and the second cardiac site is the left ventricle of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the first cardiac site is the right atrium of theheart and the second cardiac site is the left ventricle of the heart.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the excitable tissue control device is implanted inthe patient.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the excitable tissue control device is disposed outof the patient and is operatively connected to the plurality ofelectrodes implanted in or about the heart of the patient.

There is also provided, in accordance with a preferred embodiment of thepresent invention, an excitable tissue control device for setting on abeat by beat basis the parameters of an alert time window under aplurality of different cardiac conditions of a heart of a patient. Thedevice includes a plurality of electrodes implanted in or about theheart. The device also includes means for detecting electricaldepolarization events in a first cardiac site through at least a firstelectrode disposed in or about the first cardiac site, and for detectingelectrical depolarization events in a second cardiac site through atleast a second electrode disposed in or about the second cardiac site.The device also includes excitable tissue control means for deliveringnon-excitatory excitable tissue control signals to at least part of thesecond cardiac site through one or more electrodes of the plurality ofelectrodes. The device also includes memory means for storing a set ofdata. The set of data includes a plurality of sets of alert time windowparameters. Each set of alert time window parameters is uniquelyassociated with a different set of values of a plurality of cardiaccondition defining parameters identifying one of the plurality ofdifferent cardiac conditions. Each set of alert time window parametersincludes at least a set of timing parameters usable for obtaining abeginning time point and an ending time point for the alert time window.Each set of alert time window parameters is obtained by processing datacollected from a plurality of cardiac beats of the heart of the patientunder the plurality of different cardiac conditions within a datacollection session performed in the patient. The device also includesprocessing means operatively connected to the detection means, theexcitable tissue control means and the memory means. The processingmeans are used for receiving detection signals from the detection means,for controlling the excitable tissue control means by using the receiveddetection signals, for updating in a current beat cycle of the heart thevalues of a plurality of cardiac condition defining variablescorresponding to the cardiac condition defining parameters, forautomatically selecting for the current beat cycle a current set ofalert time window parameters of the plurality of sets of alert timewindow parameters based on the current values of the cardiac conditiondefining variables, for applying the current set of alert time windowparameters to start the alert time window within the current beat cycleafter detecting a first depolarization event at or about the firstcardiac site and to terminate the alert time window, and for initiatingthe delivery of a delayed excitable tissue control signal at or aboutthe second cardiac site upon detecting within the duration of the alerttime window a depolarization event in or about the second cardiac siteof the heart. The device also includes a power source for providingpower to the detection means, the processing means the memory means andthe excitable tissue control means.

Furthermore, in accordance with another preferred embodiment of thepresent invention, the device further includes telemetry meansoperatively connected to the power source and the processing means fortelemetrically receiving data from a second telemetry means disposedoutside the patient.

Finally, in accordance with another preferred embodiment of the presentinvention, the device further includes pacing means operativelyconnected to the power source, the processing means and to at least oneelectrode of the plurality of electrodes, for delivering pacing pulsesto the heart through the at least one electrode.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings, in which like components aredesignated by like reference numerals, wherein:

FIG. 1 is a schematic diagram representing a typical lead placementconfiguration of a pacemaker/ETC device within the heart, in accordancewith a preferred embodiment of the present invention;

FIG. 2 is a schematic diagram useful in understanding a method using analert window for timing the delivery of ETC signals useful in operatingthe device of FIG. 1, in accordance with a preferred embodiment of thepresent invention;

FIG. 3A is a schematic diagram illustrating a system for determining andprogramming alert window parameters for an implanted ETC device orpacemaker/ETC device, in accordance with a preferred embodiment of thepresent invention;

FIG. 3B is schematic functional block diagram illustrating the detailsof an implantable device for pacing the heart, for delivering ETCsignals to the heart and for data acquisition and processing usable asthe implantable device of the system of FIG. 3A, in accordance with apreferred embodiment of the present invention;

FIG. 4 is schematic functional block diagram illustrating the details ofanother implantable device for delivering ETC signals to the heart andfor data acquisition and processing which is usable as the implantabledevice of the system of FIG. 3A, in accordance with another preferredembodiment of the present invention;

FIG. 5 is a schematic diagram illustrating a system for pacing theheart, for delivering non-excitatory ETC signals and fornon-telemetrically determining and programming alert window parametersfor an ETC device or pacemaker/ETC device, in accordance with anotherpreferred embodiment of the present invention;

FIG. 6 is a schematic functional block diagram illustrating a system 70for delivering non-excitatory ETC signals and for non-telemetricallydetermining alert window parameters for use in an ETC device, inaccordance with another preferred embodiment of the present invention;

FIG. 7 is a schematic diagram illustrating the structure of a typicaldata collection time interval useful in the acquisition of datahistograms, in accordance with a preferred embodiment of the presentinvention;

FIG. 8A is a schematic diagram illustrating the general steps of amethod for collecting time histogram data sets under various cardiacconditions and for determining one or more sets of alert windowparameters or one or more and one or more detection parameter sets fromthe histogram data, in accordance with a preferred embodiment of thepresent invention;

FIGS. 8B and 8C are schematic flow control diagrams illustrating thesteps of a data collection method for collecting time histogram datasets in detail, in accordance with a preferred embodiment of the presentinvention;

FIG. 9 is a schematic graph illustrating a typical cumulativedistribution of cardiac cycle length;

FIG. 10 is a schematic diagram illustrating the steps of the method ofupdating the value of the logical variable ETC of FIGS. 8B-8C;

FIGS. 11A and 11B are schematic control flow diagrams of the mainprogram implementing the method for analyzing acquired data histograms,in accordance with a preferred embodiment of the present invention;

FIG. 12 is a schematic flow control diagram illustrating the steps ofthe sensitivity level determining procedure used in the main program ofFIGS. 11A-11B;

FIGS. 13A-13C are schematic flow control diagrams illustrating the stepsof the window position determining procedure used in FIGS. 11A, 11B andin FIG. 12;

FIG. 14 is a schematic flow control diagram representing the steps of aprocedure for determining the sum of the number of detected eventsstored in a given data histogram, in accordance with a preferredembodiment of the present invention;

FIG. 15 is a schematic flow control diagram illustrating the steps of aprocedure for determining the value of a variable N usable in the windowposition determining procedure of FIG. 13A-13C;

FIG. 16 is a schematic flow control diagram illustrating the steps of agroup sorting procedure usable in the window position determiningprocedure of FIGS. 13A-13C, in accordance with a preferred embodiment ofthe present invention;

FIG. 17 is a schematic flow control diagram illustrating the steps ofthe group enlarging procedure usable in the window position determiningprocedure of FIGS. 13A-13C, in accordance with a preferred embodiment ofthe present invention;

FIG. 18 is a schematic flow control diagram illustrating the steps ofthe group shrinking procedure usable in the window position determiningprocedure of FIG. 13B, in accordance with a preferred embodiment of thepresent invention;

FIG. 19 is schematic flow control diagram illustrating the steps of thecommon window position parameters determining procedure usable in themain data analysis program of FIGS. 11A-11B, in accordance with apreferred embodiment of the present invention;

FIG. 20 is a schematic graph useful for understanding a method forcomputing a set of approximation parameters useful for the real timecomputing of the alert window parameters, in accordance with a preferredembodiment of the present invention;

FIG. 21 is a schematic flow control diagram illustrating the steps of anexemplary procedure for determining the real time window approximationparameters of FIG. 19, in accordance with one preferred embodiment ofthe present invention;

FIG. 22 is a schematic control flow diagram illustrating the steps of amethod for real time setting of the beginning and ending time points ofan alert window and of the detection parameters in an ETC device havingpacing capabilities, in accordance with a preferred embodiment of thepresent invention;

FIGS. 23A-23B are schematic flow control diagrams illustrating the stepsof a method for acquiring time histogram data sets under various cardiacconditions in the absence of artificial cardiac pacing and fordetermining one or more sets of alert window parameters or approximationparameters and one or more detection parameter sets from the histogramdata, in accordance with a preferred embodiment of the presentinvention; and

FIG. 24 is a schematic control flow diagram illustrating the steps of amethod for real time setting of the beginning and ending time points ofan alert window and of the detection parameters in a non-pacing ETCdevice, in accordance with another preferred embodiment of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

Notation Used Throughout

The following notation is used throughout this document.

Term Definition RV Right ventricle LV Left ventricle SE Sensed Event PEPaced Event ETC Excitable Tissue Control PVC Premature VentricularContraction IEGM Intra-cardiac Electrogram SVC Superior Vena Cava GCVGreat Cardiac Vein CS Coronary Sinus PAC Premature Atrial Contraction

Method of timing of ETC signal delivery

Typically, ETC signal delivery is timed relative to a sensed signalrepresenting the depolarization wave locally sensed at or near the siteof the electrodes used for ETC signal delivery. This signal may be abiphasic or polyphasic intra-cardiac electrogram (IEGM) signal sensed bya lead or catheter including one or more electrodes capable of sensingan IEGM signal and of delivering pacing pulses. The depolarization waverepresented by the IEGM is an electrical event caused by spreadingmyocardial electrical excitation evoked by the natural pacemaker of theheart (normally the Sino-atrial node) in which case the event isreferred to as a sensed event (SE), or by a pacing pulse delivered tothe myocardium by, in which case the event is referred to as a pacedevent (PE). The IEGM signal may also include electrical depolarizationscaused by ectopic myocardial activation such as premature atrialcontractions (PAC) or premature ventricular contraction (PVC).Furthermore, the IEGM signal may include artifacts caused by electricalnoise.

Reference is now made to FIG. 1 which is a schematic diagramrepresenting a typical lead placement configuration of a pacemaker/ETCdevice within the heart, in accordance with a preferred embodiment ofthe present invention. The term pacemaker/ETC device generally refersthroughout the present application to a device capable of pacing a heartand of delivering non-excitatory ETC signals to the heart. ThePacemaker/ETC device 1 includes an implantable housing or case 3 forhousing the electronic circuitry 5 (not shown in detail in FIG. 1) ofthe device 1. A pacing/sensing lead 2 is suitably connected to the case3 and operatively connected to the circuitry 5.

The lead 2 includes an electrode 2A applied to the right atrium (RA) 8.The electrode 2A is used for sensing SEs and for delivering pacingpulses if necessary. The left atrium 7 (LA) is also shown in FIG. 1. Thepacing lead 2 may be inserted into the RA 8 through the subclavian veinand the superior vena cava (SVC), but other methods of insertion arealso possible. Another pacing/sensing lead 4 is connected to the case 3and operatively connected to the circuitry 5. The lead 4 includes anelectrode 4A which is applied the right ventricle (RV) 9 and is used forsensing right ventricular SEs and PEs and for delivering pacing pulsesif necessary. The lead 4 may be inserted into the RV through thesubclavian vein and the superior vena cava (SVC), but other methods ofinsertion are also possible. A third lead 6 is also suitably connectedto the case 3 and operatively connected to the circuitry 5. The lead 6includes an electrode 6A which is applied to the wall of a lateral veinof the great cardiac vein (GCV) and is used for local sensing of SEs andPEs in the left ventricle (LV) 10 and for delivering non-excitatory ETCsignals to the LV 10 if required.

The lead 6 may be inserted through the sub-clavian vein, passing throughthe SVC, the right atrium, the coronary sinus (CS) and the GCV andreaching a lateral vein of the GCV, but other methods of insertion ofthe leads 6 into or about the left ventricle (LV) are also possible. Theimplantable case 3 is typically implanted in a thoracic sub-cutaneouspocket (not shown), but other implantation positions are also possible.It is noted that the above disclosed lead placements and insertion pathsand the case placement are given by way of example only and that otherelectrode placements and lead insertion paths and case placements arealso possible.

It is noted that while each of the single electrodes 2A, 4A and 6A ofthe device 1 of FIG. 1 may be used for sensing with respect to a commonreference point such as the case 3 of the device 1, other preferredembodiments of the present invention may use pairs of locally appliedelectrodes (not shown) which may be used for local differential sensing.For example, The lead 2 may include a pair of electrodes (not shown)which are applied to the RA 8 for local sensing, the lead 4 may includea pair of electrodes (not shown) which are applied to the RV 9 for localsensing and the lead 6 may include a pair of electrodes (not shown)which are applied to the LV 10 for local sensing.

It is further noted that while the electrode 2A of the lead 2 is usedfor both sensing and pacing the RA 8, in other preferred embodiments ofthe present invention the lead 2 may include additional electrodes orelectrode pairs (not shown) such that one or more electrode or electrodepair is used for sensing in the RA 8 while other separate electrode(s)or electrode pairs are used for pacing the RA 8. Similarly, Inaccordance with a preferred embodiment of the present invention, Thelead 4 may include more than one electrode or pair of electrodes (notshown) which may be separately used for sensing and for pacing the rightventricle 9. Yet similarly, The lead 6 may include more than oneelectrode or electrode pairs (not shown) of which one or more electrodeor electrode pair is used for sensing in the left ventricle 10 and oneor more additional electrodes or electrode pairs are used for deliveringnon-excitatory ETC signals to the left ventricle 10.

It will therefore be appreciated by those skilled in the art, that thenumber and arrangement of the electrodes within the leads 2,4 and 6 maybe varied in many ways and many combinations all being within the scopeand spirit of the present invention.

Various types of electrodes and electrode positioning methods known inthe art may be used for sensing and pacing and for delivering ETCsignals to the heart. One or more of the electrodes or electrode pairs2A, 4A and 6A may be implanted within a cardiac chamber and placed incontact with the endocardium as disclosed hereinabove. One or more ofthe electrodes or electrode pairs 2A, 4A and 6A may also be disposedwithin a cardiac blood vessel, such as a lateral vein of the GCV oranother suitable cardiac blood vessel, and used for sensing and/orpacing and/or delivering ETC signals to the myocardial tissue adjacentto or in contact with the blood vessel wall. One or more of theelectrodes or electrode pairs 2A, 4A and 6A may also be epicardialelectrodes which may be epicardially applied to the heart as is wellknown in the art.

Typically, ETC signals are delivered to the left ventricle via theelectrode(s) 6A of lead 6. The timing of the ETC signal is triggered bylocally sensing in the LV the depolarization wave of the PE or the SE.Preferably, a separate sensing electrode (not shown) which is alsoincluded within the lead 6 and is positioned in the vicinity of theelectrode(s) 6A, is used for the local sensing in or about the LV 10,since the type and surface area optimal for sensing electrodes areusually different than the type and surface area of electrodes which areoptimized for delivering the relatively large currents of ETC signals.However, It may also be possible to use the same electrode (orelectrodes) 6A for delivering the ETC signal and for locally sensing thedepolarization wave in or about the LV 10.

To facilitate correct timing of the ETC delivery, measures need to betaken so that ETC signal delivery is not triggered by local LV sensingof noise, premature ventricular contractions (PVCs), premature atrialcontractions (PACs) or by delayed sensing of remote events such as aright ventricular depolarization. One possible approach is therestricting of the local sense triggering for ETC delivery to apredefined time window.

The use of a predefined time window for other different purposes such asto detect activation for capture verification in pacemakers is known inthe art. U.S. Pat. No. 5,443,485 to Housworth et al. discloses the useof a timing window to detect a paced stimulation pulse for achievingcapture verification to ensure that the pacing pulse energy is highenough.

U.S. Pat. No. 5,683,431 to Wang discloses a method for performingpacemaker capture verification using electrodes different than thepacing electrodes to sense the activation evoked by the pacing pulse.

U.S. Pat. No. 5,391,192 to Lu et al. discloses a method for externallydetermining the minimum energy of a pacing pulse for captureverification using window based detection of activation.

Reference is now made to FIG. 2 which is a schematic diagram useful inunderstanding a method using an alert window for timing the delivery ofETC signals useful in operating the device of FIG. 1, in accordance witha preferred embodiment of the present invention. The detection timewindow is referred to as the “alert window” throughout the presentapplication.

The horizontal axis of FIG. 2 represents time. The arrow labelled 11schematically represents the timing of a depolarization event 11 locallysensed in the RV by one or more electrodes (not shown) of the lead 4 ofFIG. 1. The time T₀ represents the time of detection of the RV event.Typically, the time T₀ represents the time point at which a thresholdcrossing occurs. However, T₀ may also represent the time of eventdetection obtained by other methods known in the art for cardiac eventdetection such as detection methods based on the shape of the signal(also known as signal morphology based detection methods) or othersuitable detection methods known in the art. The RV event 11 mayrepresent a locally sensed RV depolarization initiated by a naturallyoccurring SA node evoked atrial event (not shown) or initiated byartificial atrial pacing. The RV event 11 may also represent a locallysensed RV depolarization initiated by a pacing pulse delivered to the RVthrough an electrode (not shown) included in the lead 4 of FIG. 1. Afterthe time T₀, a local sense “refractory” period labeled ΔT1 begins. Therefractory period ΔT1 ends at time T_(R). During the refractory periodΔT1 no sensing is performed. This refractory period is used to avoid theelectrical pacing artifact due to electrode polarization and/orelectrode cross-talk. The refractory period may also be useful inavoiding electrical artifacts due to far field sensing as is well knownin the art.

Typically, the duration of the refractory period ΔT1 is approximately10-15 milliseconds but other values may be used depending, inter alia,on the specific application, electrode type, and detection method used.It is noted that, in accordance with one preferred embodiment of thepresent invention, the value of the refractory period duration may beset to ΔT1=0. In such an embodiment no refractory period ΔT1 isimplemented.

A local sense alert window having a duration ΔT3 starts at time T₁ andends at time T₃. The time interval between time points T₀ and T₁ isdefined as the alert window delay interval ΔT2 which is the delaybetween time of detection of the depolarization event 11 and thebeginning of the alert window ΔT3.

The arrow labeled 12 of FIG. 2 schematically represents the occurrenceof a depolarization event locally sensed in the LV. For example, thelocally sensed event 12 may be sensed by a sensing electrode (not shown)or by an ETC signal delivery electrode (not shown) included within thelead 6 of FIG. 1. The time T₂ represents the time of detection of the LVdepolarization event 12. Typically, the time T₂ represents the timepoint at which a threshold crossing occurs as is disclosed hereinbelow.However, T₂ may also represent the time of event detection obtained byother methods known in the art for cardiac event detection.

An article titled “NEURAL NETWORK BASED ADAPTIVE MATCHED FILTERING FORQRS DETECTION” by Xue et al., published in IEEE Transactions onBiomedical engineering, Vol. 39, No. 4 pp. 317-329 (1992) andincorporated herein by reference, discloses an adaptive matchedfiltering algorithm based on an artificial neural network for QRSdetection.

An article titled “IDENTIFICATION OF VENTRICULAR TACHYCARDIA WITH USE OFTHE MORPHOLOGY OF THE ENDOCARDIAL ELECTROGRAM” by Langberg et al.,published in Circulation, Vol. 77, No. 6 pp. 1363-1369 (1988) andincorporated herein by reference, discloses the application of atemplate to derive morphological parameters of unipolar and bipolarelectrogram signals for detecting tachycardia.

An article titled “CLASSIFICATION OF CARDIAC ARRHYTHMIAS USING FUZZYARTMAP” by F. M. Ham and S. Han, published in IEEE Transactions onBiomedical engineering, Vol. 43, No. 4 pp. 425-430 (1996) andincorporated herein by reference, discloses the use of a fuzzy adaptiveresonance theory mapping (ARTMAP) neural net classifier for classifyingQRS complexes under normal and abnormal conditions.

U.S. Pat. No. 5,782,876 to Flammang titled “METHOD AND APPARATUS USINGWINDOWS AND AN INDEX VALUE FOR IDENTIFYING CARDIAC ARRHYTHMIAS”,incorporated herein by reference, discloses the use of the sensedelectrogram slope (derivative of ECG) for morphological electrogramdetection in a device for identifying cardiac arrhythmias.

The above referenced morphological signal detection methods, as well asother signal morphology based detection methods known in the art, may beadapted for detection of the depolarization events within the IEGMsignals of the present invention.

The detection of the LV sensed event 12 at time T₂ triggers the deliveryof an ETC signal represented by the cross hatched area labeled ETC. TheETC signal starts at a time point T₄ separated from T₂ by a delayinterval ΔT4. The ETC signal has a duration ΔT5.

Preferably, the value of the duration of the ETC signal ΔT5 is avariable duration and may vary from one beat cycle to another inaccordance with the required modification of myocardial contractility.Typically, the duration and or other parameters of the ETC signal may bemodified based on the current value of the heart rate. The methods fordetermining the required ETC signal duration ΔT5 are not the subjectmatter of the present invention and will not be disclosed in detailhereinafter.

It is noted that, in accordance with other preferred embodiments of thepresent invention, the duration of the ETC signal ΔT5 may be a constantvalue which does not vary from one beat cycle to another beat cycle.

The ETC signals may have various waveforms, durations and intensities asdisclosed in detail by Ben Haim et al. in the above referencedInternational Publications No. WO 97/25098, WO 98/10828, WO 98/10829, WO98/10830, WO 98/10831 and WO 98/10832. The characteristics of thedelivered ETC signals are not the subject of the present invention andwill not be further discussed hereinafter.

Only a locally sensed depolarization event detection occurring withinthe duration of the alert window ΔT3 is used to trigger an ETC signal.The detection of an electrical depolarization event happening outsidethe alert window will not result in triggering of an ETC signal. Thishas the advantage of reducing the probability of delivering animproperly timed ETC signal due to electrical noise occurring outsidethe preset duration of the alert window ΔT3. However, if adepolarization event (not shown) due to an ectopic beat is detectedbetween the time T₀ and the time T₁ in a case where the refractoryperiod ΔT1 is not used, or between the time T_(R) and the time T₁ in acase where the refractory period ΔT1 is used, and then a laterdepolarization event (not shown) is detected within the duration of thealert window ΔT3, the triggering of an ETC signal by the later occurringdepolarization event may result in an improperly timed ETC signal.Therefore, In order to prevent such improper timing, the timing methodmay further include an inhibitory window ΔTI. Any depolarization eventwhich is detected within the duration of the inhibition window ΔTI willresult in the inhibiting of ETC signal delivery within the current beatcycle as disclosed in detail hereinbelow.

In accordance with one preferred embodiment of the present invention,ΔTI=ΔT2−ΔT1, in such a preferred embodiment the inhibition window ΔTIstarts at the end of the refractory period ΔT1 and ends at the beginningof the alert window ΔT3. If no refractory period is used (ΔT1=0), theinhibition window spans the entire alert window delay interval ΔT2.However, in accordance with other preferred embodiments of the timingmethod of present invention, the end of the inhibition period ΔTI may beseparated from the beginning of the alert window ΔT3 by an intermediatetime interval (not shown in FIG. 2 for the sake of clarity ofillustration). The detection of a depolarization event within theduration of such an intermediate time interval will not result in theinhibition of triggering of an ETC signal by a later depolarizationevent detected within the duration of the alert window ΔT3.

If a depolarization event was detected in the IEGM signal which islocally sensed in the left ventricle 10 within the duration of theinhibition window ΔTI, ETC signal delivery is inhibited such that lateroccurrence of a depolarization event within a preset “inhibitionrefractory period” (not shown in FIG. 2 for the sake of clarity ofillustration) of the current beat cycle will not result in a delivery ofan ETC signal. This feature has the advantage that it reduces theprobability of erroneous detection of spurious noise or of ectopic beatssuch as PVCs or PACs and the subsequent triggering of the delivery of anincorrectly timed ETC signal. The details of the implementation of theinhibition refractory period are disclosed in detail in co-pending U.S.patent application to Mika et al., Ser. No. 09/276,460, Titled“APPARATUS AND METHOD FOR TIMING THE DELIVERY OF NON-EXCITATORY ETCSIGNALS TO A HEART”, filed Mar. 25, 1999.

Typically, the local sensing sensitivity is adjusted such that, onlyevents of a certain amplitude will be detected. This is achieved bysetting a detection threshold. Threshold crossing detection methods forelectrical signals are well known in the art and are not the subjectmatter of the present invention. Such threshold crossing detectionmethods are commonly used in pacemakers for sensed event detection.

Briefly, any acceptable detection method based on threshold crossing ofone or more threshold levels may be used with the present invention. Forexample, the sensed electrogram may be biphasic, and two thresholdlevels may be used including a positive threshold level and a negativethreshold level. Alternatively, full wave rectification of theelectrogram may be used to obtain a signal which is positive only, suchthat a single positive threshold level may be used. Additionally, othermethods of detection may be used which are based on signal morphology asdisclosed in detail hereinabove.

Since multiple threshold crossings may occur during the samedepolarization event or during noise signals, ambiguity may arise as towhich threshold crossing should be used as the trigger. This may besolved by triggering by the first threshold crossing in the window andby implementing an “alert refractory period” ΔT7 following the firstthreshold crossing of the LV sensed event 12 at time T₂ to preventmultiple triggering by multiple threshold crossings occurring within asingle depolarization wave representing a single event. The alertrefractory period ΔT7 starts at the time T₂ and has a fixed durationrepresented by the double headed arrow labeled ΔT7. During the alertrefractory period ΔT7 no sensing is performed so that additionaltriggering cannot happen during the period ΔT7.

It is noted that, since the first threshold crossing due to an LV sensedevent 12 may happen at any time during the alert window ΔT3, and sincethe duration of the ETC signal ΔT5 may be varied from one beat cycle toanother (for varying the effects of the ETC signal on myocardialcontraction), the duration of the alert refractory period ΔT7 is setsuch that it is larger than the sum of the durations of the alert windowΔT3, the delay interval ΔT4 and the maximal allowable duration ΔT5_(MAX) of the ETC signal. The maximal allowable duration ΔT5 _(MAX) is apreset value.

Thus, ΔT7>ΔT3+ΔT4+ΔT5 _(MAX). This ensures that no further thresholdcrossings will be sensed and detected after the first threshold crossingdetection until the ETC signal has ended, irrespective of the time ofoccurrence of the first threshold crossing detection T₂ within the alertwindow duration ΔT3 and of the specific duration ΔT5 of the ETC signaldelivered within the current beat cycle.

Typically, the duration ΔT3 of the alert window is approximately 30milliseconds, the duration of the delay interval ΔT4 is approximately 60milliseconds and the maximal allowable duration ΔT5 _(MAX) of the ETCsignal is approximately 20-30 milliseconds. However, other values ofΔT3, ΔT4 and ΔT5 _(MAX) may be used.

A typical value of the duration of the alert refractory period ΔT7 istherefore approximately 150-200 milliseconds. However, other values ofthe duration of the alert refractory period ΔT7 may be used depending,inter alia, on the particular values of ΔT3 , ΔT4 and ΔT5 _(MAX) used.The duration of the alert refractory period ΔT7 is a preset value anddoes not change from one beat cycle to another. However, The duration ofthe alert refractory period ΔT7 may be changed if necessary byappropriately reprogramming the software embedded within the device 1telemetrically or non-telemetrically (depending on the specific hardwareimplementation of the device 1).

For the sake of simplicity of presentation, the method of the presentinvention will be disclosed as using a single positive threshold level.A certain positive threshold voltage level is set for the pacemaker/ETCdevice. A crossing of this threshold level by the IEGM signal occurringwithin the time interval between T_(R) and T₃ will be detected as anevent. For example, the detection threshold may be set as +3.0millivolts but other suitable threshold levels may also be used fordetection, depending, inter alia, on the placement and quality ofcontact of the sensing electrode or electrodes with the cardiac site atwhich the sensing is performed. A refractory period of approximately150-200 milliseconds starting at the time of detection of thresholdcrossing, may be used to prevent multiple threshold crossing detections,but other suitable values of the sense refractory period may also beused. In accordance with one preferred embodiment of the presentinvention, the use of the refractory period may be implemented asdisclosed in detail in the above referenced co-pending U.S. patentapplication to Mika et al., Ser. No. 09/276,460, Titled “APPARATUS ANDMETHOD FOR TIMING THE DELIVERY OF NON-EXCITATORY ETC SIGNALS TO AHEART”.

In accordance with another preferred embodiment of the presentinvention, the ETC device or pacemaker/ETC device of the presentinvention may continuously perform morphological analysis on the IEGMsignal locally sensed in or about the left ventricle (or at a cardiacsite in the vicinity of the cardiac site at which the ETC signal is tobe delivered) for the entire duration of the alert window period, andthe decision as to which of the depolarization events (provided thatthere was more than one such depolarization event within the alertwindow duration) is to be used as the ETC signal triggering event may bemade based on the results of the morphological analysis which determinethe depolarization event which gives the best match according withpredetermined morphological criteria. After determining the event whichis to be used as the ETC signal trigger, the timing of the delivery ofthe ETC signal is determined as disclosed in detail by Mika et al. Inthe co-pending U.S. patent application, Ser. No. 09/276,460 citedhereinabove.

It will be appreciated that any suitable method of morphologicalanalysis known in the art including but not limited to the methodsdisclosed by Xue et al., Langberg et al., Ham and Han, and Flammang, maybe used for morphological analysis in the method of the presentinvention, provided that the processor or controller used in the ETCdevice or pacemaker/ETC device has sufficient processing power.

It is noted that, many other suitable methods of event detection,including but not limited to the methods of using IEGM single thresholdcrossing, IEGM multiple threshold crossings, IEGM derivative (for signalslope determination), signal morphology detection methods orcombinations thereof may be used in the ETC signal timing method of thepresent invention.

The conduction characteristics of the myocardium of a patient may varyconsiderably. Among the factors influencing the conduction velocity ofthe myocardium are electro-physiological changes induced in themyocardium due to patient exercise, increased metabolic activity orstress. These changes may be mediated, inter alia, by noradrenaline andother hormones which are released into the circulation and affect themyocardial conduction velocity or by sympathetic (or parasympathetic insome cases) neural control of cardiac tissue. Such mechanisms may leadto changes in the heart rate through their effects on the natural SAnode pacemaker. Thus, under conditions of patient exercise, increasedmetabolic activity or stress, the heart rate increases and theconduction velocity of the myocardial depolarization wave increases.This increase in conduction velocity causes the electrogram signalsensed in the LV by the lead 6 (FIG. 1) to be shifted in time such thatthe time interval T₂−T₀ decreases and may be smaller than T₁ whichresults in the locally sensed event 12 falling outside of the alertwindow and within the inhibition window ΔTI, which will lead to activeinhibition of the delivery of the ETC signal. Slowing of the heart ratemay cause the IEGM signal sensed in the LV by the lead 6 (FIG. 1) to beshifted in time such that the time T₂ of occurrence of the locallysensed event 12 occurs later within the alert window ΔT3 of FIG. 2, oroccurs at a time point later than the time point T₃, which is outside ofthe alert window ΔT3 in which case no triggering will occur.

Additionally, the conduction velocity of a paced event in the myocardiumis slower than the conduction velocity of the depolarization wave evokedby a naturally evoked sinus rhythm.

Another factor influencing the myocardial conduction velocity is thedelivery of ETC signals to the myocardium. During the application of ETCsignals to the myocardium the conduction velocity of myocardialdepolarization may be modified. The conduction velocity may be increasedor decreased depending, inter alia, on the type of ETC signal which isdelivered to the myocardium.

Thus, the conduction velocity and consequently the time interval betweenthe RV sensed event and the LV sensed event are heart rate dependent andmay depend on other cardiac conditions.

In accordance with one embodiment of the present invention, the methodof timing of the delivery of the ETC signal uses a fixed alert windowdelay period (ΔT2) and a fixed alert window duration (ΔT3) which is wideenough to enable acceptably accurate detection under a variety ofconditions involving different myocardial conduction velocity values. Asingle set of alert window parameters is determined which includes thedetection threshold value used for triggering within the alert window,the alert window starting time point T₁ and the alert window end timepoint T₃. This alert window parameter set is determined such as toenable an acceptable level of detection of events for all or most of theconditions involving different myocardial conduction velocity values.The pacemaker/ETC device 1 may then be programmed with this determinedsingle set of alert window parameters as is disclosed in detailhereinafter. In this preferred embodiment of the present invention, oncethe alert window parameters are determined, the implanted pacemaker/ETCdevice 1 is programmed with these parameters and uses the same set ofalert window parameters for the timing of the delivery of the ETCsignals as disclosed hereinabove. The above cited co-pending U.S. patentapplication to Mika et al., Ser. No. 09/276,460, titled “APPARATUS ANDMETHOD FOR TIMING THE DELIVERY OF NON-EXCITATORY ETC SIGNALS TO AHEART”, discloses a method and apparatus for timing the delivery of ETCsignals to a heart using an alert window having preset fixed parameters.

However, it may be advantageous to use a plurality of different sets ofalert window parameters. The use of a plurality of different alertwindow parameters is desirable since excessive widening of the alertwindow duration which may be required for suitable event detection undera variety of different patient cardiac conditions when a single alertwindow parameter set is used, may result in an increased probability ofspurious detection of noise and/or ectopic events. In contrast, when aplurality of alert window parameter sets are used, the delay andduration of each specific alert window may be better adapted to aparticular patient condition, such as but not limited to a particularheart rate, by modifying the alert window parameters sufficiently toposition the alert window at the time period most proper for eventdetection to acceptably reduce the probability of detection of spuriousnoise and/or ectopic events.

Each set of alert window parameters includes data which may be used tocalculate in real time the values of T₁ and T₃ which are optimized for aspecific condition or for a specific range of conditions. The data ofeach set are determined so as to optimize detection of LV locally sensedevents under the specific condition without unduly increasing spurioustriggering. This method may be of particular advantage in patients inwhich the myocardial conduction velocity substantially varies betweenthe different conditions disclosed hereinabove and in which the use of asingle set of alert window parameters may lead to significantinaccuracies in the detection of the locally sensed event or in thetiming of the ETC signal delivery during at least one of the variousdifferent conditions leading to changes of myocardial conductionvelocity disclosed hereinabove. Such inaccuracies may occur due to ashift of the time of occurrence of the LV locally sensed event which mayincrease the probability of such a sensed event occurring out of thealert window time interval. This will cause a certain percentage of theLV locally sensed events to go undetected, so that not every LV locallysensed event will trigger the delivery of an ETC signal. While this maynot by itself endanger the patient, it may lead to a reduction in thedesired effect of the ETC signal on cardiac contractility. However, theuse of a single common set of window parameters under varying conditionsmay result in increased rate of incorrect triggering of ETC signaldelivery by spurious noise or by PVCs. This may lead to delivery of ETCsignals outside of the inexcitable myocardial period which may bearrhythmogenic.

Therefore, in accordance with another preferred embodiment of thepresent invention, the implanted device 1 is programmed with a pluralityof predetermined alert window parameter sets. Each of the predeterminedparameter sets includes data for computing the values of T₁ and T₃ ofthe alert window in real time and may also include a detection thresholdvalue. If a detection method using morphological IEGM parameters is usedthe alert window parameter sets may also include morphological parameterdata useful for detecting a depolarization event. Each set of alertwindow parameters is optimized for use under specific conditions. Forexample, different alert window parameter sets may be used for differentranges of heart rates as is disclosed in detail hereinafter. Otherdifferent sets of alert window parameters may be used for paced events,sensed events, and for events occurring in periods during which ETCsignals are delivered to the myocardium.

Systems and methods for determining alert window parameters

The present invention discloses, inter alia, systems and methods fordetermination of the alert window parameters.

Reference is now made to FIG. 3A which is a schematic diagramillustrating a system for determining and programming alert windowparameters for an implanted ETC device or pacemaker/ETC device, inaccordance with a preferred embodiment of the present invention. Thesystem 20 includes an implanted ETC device 19 and an analyzing unit 23.The implanted ETC device 19 further includes electronic circuitry (notshown in FIG. 3A for the sake of clarity of illustration) for eventsensing and for delivering ETC signals, the details of such circuitryare disclosed in detail hereinafter. The implanted ETC device 19 may ormay not include pacing circuitry (not shown in FIG. 3A for the sake ofclarity of illustration) for pacing the heart as is disclosed in detailhereinafter. The implanted ETC device 19 is suitably connected to one ormore implantable leads 22 and includes a telemetry unit 26 forwirelessly communicating with the analyzing unit 23. The analyzing unit23 includes a telemetry unit 28 for wirelessly communicating with thetelemetry unit 26 of the pacemaker/ETC device 19. The analyzing unit 23further includes a processing unit 30 in communication with thetelemetry unit 28 for receiving data from the telemetry unit 28 and forstoring and processing the received data. The analyzing unit 23 furtherincludes a display unit 32 suitably connected to the processing unit 30for displaying graphic symbolic and numerical data processed by theprocessing unit 30. The processing unit 30 may be a computer, a personalcomputer, a workstation, a mainframe or any other type of computingdevice capable of storing and processing data. The display unit 32 maybe a cathode ray tube (CRT) display, a video monitor, an LCD display orany other suitable type of display or monitor. The analyzing unit 23further includes one or more user interfaces 31 for enabling a user suchas a cardiologist or another operator to control the operation of theanalyzing unit 23. The user interface 31 may be a keyboard, a pointingdevice or any other suitable user interface device or a combination ofuser interface devices which are known in the art.

Reference is now made to FIG. 3B which is schematic functional blockdiagram illustrating the details of an implantable device for pacing theheart, for delivering ETC signals to the heart and for data acquisitionand processing usable as the implantable device of the system of FIG.3A, in accordance with a preferred embodiment of the present invention.The implantable pacemaker/ETC device 21 is a preferred version of theimplantable device 19 of FIG. 3A suitable for use within the system 20of FIG. 3A The pacemaker/ETC device 21 includes a pacing core 34 forproviding pacing pulses to the RA and RV pacing electrodes (not shown)of the implantable leads 22. The pacemaker/ETC device 21 furtherincludes sense amplifier units 36 for amplifying the RA, RV and LVsignals locally sensed by the sensing electrodes (not shown) of theimplantable leads 22. For example, when the pacemaker/ETC device 21represents the pacemaker/ETC device 1 of FIG. 1, one of the senseamplifier units 36 receives the signal locally sensed in the RA 8 fromlead 2 of FIG. 1, another of the sense amplifier units 36 receives thesignal locally sensed in the RV 9 from lead 4 of FIG. 1 and a third oneof the sense amplifier units 36 receives the signal locally sensed inthe LV 10 from the lead 6 of FIG. 1.

The pacemaker/ETC device 21 further includes sensing units 38 suitablyconnected to a controller unit 40. The sensing units 38 receive theamplified locally sensed signals from the amplifier units 36 and providetrigger signals to the controller unit 40 for activating the pacing coreas is known in the art. The pacemaker/ETC device 21 further includestiming units 42, connected to the controller unit 40 for providing thecontroller unit 40 with clock signals, and a memory unit 44 suitablyconnected to the controller unit 40. The controller 40 can store data inthe memory unit 44 and can access the data stored in the memory unit 44for processing the accessed data and/or for sending data to a telemetryunit 26 for telemetrically communicating the data to a receiving station(not shown) placed outside of the patient. The memory unit 44 mayinclude random access memory (RAM) units (not shown), read only memory(ROM) units (not shown), other suitable type of memory units known inthe art, or any suitable combination of memory unit types.

It is noted that the pacemaker/ETC device 21 when connected toimplantable leads having the configuration of leads 2, 4, and 6 of FIG.1, may function, inter alia, as a pacemaker in a DDD mode, whichincludes, inter alia, the ability to detect PVCs by using PVC detectionmethods known in the art. For example, PVC detection may be performed bythe circuitry of the pacemaker/ETC device 21 using dual chamber eventsequence analysis methods as is known in the art. However, other methodsknown in the art for PVC detection may also be used.

The telemetry unit 26 is used for wirelessly transmitting data stored inmemory unit 44 under the control of the controller unit 40. Thepacemaker/ETC device 21 further includes an excitable tissue controller(ETC) unit 50. The ETC unit 50 is suitably connected to the controllerunit 40 and to one or more ETC electrodes (not shown) within the leads22. For example, when the pacemaker/ETC device 21 represents thepacemaker/ETC device 1 of FIG. 1, the ETC unit 50 is connected to theETC signal delivering electrode 6A of the lead 6 of FIG. 1. However inother preferred embodiments of the present invention, the ETC unit 50may be connected to one or more ETC electrodes or ETC electrode pairs(not shown) which are used for delivering ETC signals. The controllerunit 40 controls the delivery of ETC signals to the myocardium by timingthe delivery of suitable control signals to the ETC unit 50.

Reference is now made to FIG. 4 which is schematic functional blockdiagram illustrating the details of another implantable device fordelivering ETC signals to the heart and for data acquisition andprocessing which is usable as the implantable device of the system ofFIG. 3A, in accordance with another preferred embodiment of the presentinvention. The device 24 is similar to the device 21 of FIG. 3A exceptthat it does not include the pacing core 34 of the device 21 of FIG. 3Aand is not capable of pacing.

The device 24 may be used in patients where ETC signals need to bedelivered to the heart for modulating cardiac contractility but pacingof the heart is not required, such as but not limited to congestiveheart failure (CHF) patients. CHF patients may have an unimpairedcardiac conduction system and may exhibit no chronotropic incompetence.In the cases where the device 24 is used for delivering ETC signals tothe heart, the electrodes (not shown) in the implantable leads 22 areused for sensing and for delivering ETC signals and are not used forpacing the heart.

In operation, the data stored in the memory unit 44 of the devices 21and 24 of FIGS. 3A and 4, respectively, is telemetrically transmitted bythe telemetry unit 48 to the analyzing unit 23 (FIG. 3A) which isdisposed outside the patient for processing, storage and display. Thesystem 20 of FIG. 3A may graphically display the data on the displayunit 32. The displayed data is used by the user or physician todetermine the alert window parameters as is disclosed in detailhereinafter. Alternatively, the alert window parameters may beautomatically determined and displayed for approval by the user or thephysician.

In accordance with another preferred embodiment of the presentinvention, the alert window parameters may be determined bynon-telemetrically communicating the locally sensed IEGM signals sensedin a patients heart to a processing and analyzing system disposedoutside the patient.

Reference is now made to FIG. 5 which is a schematic diagramillustrating a system 60 for pacing the heart, for deliveringnon-excitatory ETC signals and for non-telemetrically determining andprogramming alert window parameters for an ETC device or pacemaker/ETCdevice, in accordance with another preferred embodiment of the presentinvention. The system 60 includes a plurality of implantable leads 22implanted within a patient (the patient is not shown) and an analyzingunit 64. The plurality of implantable leads 22 may include, for example,the leads 2, 4 and 6 of FIG. 1. However, the plurality of leads 22 mayinclude any other suitable combinations of leads including a pluralityof sensing, pacing and ETC electrodes positioned in two or more chambersof the heart as disclosed for the devices 1, 19, 21 and 24 hereinabove.

The plurality of leads 22 are implanted in the patient's heart and arethen suitably connected to the analyzing unit 64 for data acquisition tocollect data for determining the alert window parameters.

The analyzing unit 64 includes a processing unit 61, a front-end unit62, an analog to digital converting unit (A/D) 63, a pacing unit 68 andan ETC unit 65. The front end unit 62 is suitably connected to one ormore of the sensing electrodes of the leads 22 and to the processingunit 61 for pre-conditioning one or more IEGM signals sensed by theseone or more sensing electrode. The front-end unit 62 may includesuitable circuitry such as one or more amplifier circuits (not shown)for amplifying the IEGM signals sensed by the one or more sensingelectrodes. The front-end unit 62 may also include filter circuits (notshown) for filtering the amplified signals prior to digitizing them bythe A/D unit 63. The front-end unit 62 is suitably connected to the A/Dunit 63 and provides amplified or amplified and filtered IEGM signalsthereto for digitizing.

The A/D unit 63 may include one or more separate A/D converters (notshown) each A/D converter being dedicated to a single sensing electrodeof the one or more sensing electrodes. Alternatively, the A/D unit 63may include a single A/D converter (not shown) suitably connected to aplurality of sensing electrodes of the leads 22 through a multiplexerunit (not shown). The digitized IEGM signals are provided to theprocessing unit 61 by the A/D unit 63 for further processing. Theprocessing unit 61 digitally performs the detection of events based onthe digitized IEGM data provided by the A/D unit 63. The analyzing unit64 further includes a memory unit 66 suitably connected to theprocessing unit 61 for storing data.

The pacing unit 68 is suitably connected to the processing unit 61 andto one or more pacing electrodes of the leads 22. The pacing unit 68receives control signals from the processing unit 61 for controlling thedelivery of pacing pulses to one or more locations in the heart (notshown). The pacing unit 68 includes all the necessary circuitry fordelivering pacing pulses to one or more pacing electrodes. Suchcircuitry is well known in the art and is not shown in detailhereinafter.

It is noted that the analyzing unit 64 when connected to the implantableleads 22 is capable of performing all the functions of an implantedpacemaker. For example, when the leads 22 have the configuration ofleads 2, 4, and 6 of FIG. 1, the analyzing unit 64 is capable ofperforming, inter alia, all the functions of an implanted pacemaker in aDDD mode. These functions include, inter alia, the ability of detectionof PVCs as is well known in the art.

The ETC unit 65 is suitably connected to the processing unit 61 and toone or more ETC signal delivery electrodes of the implantable leads 22.The ETC unit 65 receives control signals from the processing unit 61 forcontrolling the delivery of ETC signals to the heart through the one ormore ETC delivery electrodes of the implantable leads 22.

The ETC unit 65 may be any suitable unit for delivering ETC signalshaving various waveforms, duration values and intensities as disclosedin detail by Ben Haim et al. in the above referenced InternationalPublications No. WO 97/25098, WO 98/10828, WO 98/10829, WO 98/10830, WO98/10831 and WO 98/10832. The characteristics of the delivered ETCsignals are not the subject of the present invention and will not befurther discussed hereinafter.

The system 60 further includes a display unit 32 suitably connected tothe processing unit 61 for displaying graphic symbolic and numericaldata processed by the processing unit 61 as disclosed hereinabove forthe analyzing system 20 of FIG. 3A. The system 60 may further include adata storage unit 67 for storing data. The data storage unit 67 may beany suitable data storage device for storing data on a storage mediumsuch as a magnetic storage medium, an opto-magnetic storage medium, anoptical storage medium, a holographic storage medium or any other typeof fixed or removable storage medium. Some non-limiting examples of thestorage device are, a magnetic hard disk drive, a magnetic floppy diskdrive, an opto-magnetic disk drive, an optical disc drive. The datastored on the data storage device may include, inter alia, patientclinical data, patient demographic data, various IEGM and histogram datacollected in the process of determining the alert window parameters andvarious determined alert window parameter sets. The data storage devicemay be used for storing data for a plurality of different patients.

The system 60 further includes one or more one user interface devices 69suitably connected to the processing unit 61 through a suitablecommunication interface (not shown) for enabling the user of the system60 to input data and commands for controlling the operation of theanalyzing unit 64. The user interface device(s) 69 may be a keyboard, apointing device such as a mouse, a light pen in combination with asuitable touch sensitive screen or tablet, or any other suitable devicefor inputting data or commands to the analyzing unit 64, or any suitablecombination thereof.

In operation, after the leads 22 are implanted in the heart of thepatients and are connected to the analyzing unit 64, the analyzing unit64 is operated to collect data for determining the parameter sets forthe alert window under various conditions as is disclosed in detailhereinafter. It is noted that the analyzing unit 64 is capable ofperforming all the activities of an implanted pacemaker/ETC device suchas the pacemaker/ETC device 21 of FIG. 3A except for the telemetryfunctions. The analyzing unit 64 may perform cardiac pacing at one ormore cardiac locations and may controllably deliver ETC signals to oneor more cardiac locations. The performance of the functions of apacemaker/ETC device by the analyzing unit 64 may be achieved by usingdifferent methods and/or different hardware implementation than themethods and hardware of an implantable pacemaker/ETC device. Forexample, while in the pacemaker/ETC device 21 the event detection isperformed by sensing units 38 which are analog circuits, the eventdetection in the analyzing unit 64 is performed by digitally processingthe digitized IEGM data provided by the A/D unit 63. Additionally, thepacing unit 68 and the ETC unit 65 may have hardware and softwareimplementations different than those of the pacing core 34 and the ETCunit 50, respectively, of the pacemaker/ETC device 21 because of thephysical size and current consumption limitations imposed on the designof the pacing core 34 and the ETC unit 50 of the pacemaker/ETC device21. These limitation are not relevant in the non-implanted analyzingunit 64. However, functionally, the sensing, pacing and ETC delivery ofthe analyzing unit 64 are similar to and may be regarded as simulatingthe same functions of an implanted of the pacemaker/ETC device, such as,for example, the functions of the pacemaker/ETC device 21 of FIG. 3A.Therefore, after the different alert window parameter sets aredetermined using the analyzing unit 64, these alert window parametersets may be used to program an implanted pacemaker/ETC device and areused to operate the programmed implanted pacer/ETC device after it hasbeen suitably connected to the implantable leads 22 and implanted in thepatient.

Reference is now made to FIG. 6 which is a schematic functional blockdiagram illustrating a system 70 for delivering non-excitatory ETCsignals and for non-telemetrically determining alert window parametersfor use in an ETC device, in accordance with another preferredembodiment of the present invention.

The system 70 includes an external non-implanted analyzing unit 74suitably connected to a plurality of implantable leads 22. The analyzingunit 74 of FIG. 6 is similar to the analyzing unit 64 of FIG. 5, exceptthat it does not include the pacing unit 68. The analyzing unit 74operates similarly to the analyzing unit 64, except that it does nothave the pacing capacity of the analyzing unit 64 and is therefore notcapable of pacing of the heart.

It is noted that, while the devices 1, 19, 21 and 24 of FIGS. 1,3, 3Aand 4 respectively, and the systems 60 and 70 of FIGS. 5 and 5A,respectively, may use the single threshold crossing detection methoddisclosed in detail hereinabove, all of these devices and systems mayuse other detection methods. The detection methods for detectingdepolarization events in the IEGM signals sensed by one or more of theelectrodes or electrode pairs included in one or more of the implantableleads such as the leads 2,4, and 6 of the device 1 and the plurality ofimplantable leads 22 of the devices 19, 21 and 24 and the systems 60 and70, may include any suitable detection methods known in the art fordetection of locally sensed cardiac depolarization events based onsignal morphology and/or methods based on multiple threshold crossingsand/or signal slope or any combinations thereof as disclosedhereinabove.

Typically, the data acquisition method of the present invention includesautomatically varying the detection threshold levels and cumulativelyrecording data of threshold crossing events at predefined time binsstarting at the time of detection of an RV event (T₀ of FIG. 2).

After implantation of the pacemaker/ETC device 21 the pacing parametersare set (including, inter alia, the pacing voltage, the pacing pulsewidth, and other relevant pacing parameters), data acquisition andprocessing will take place as explained hereinbelow. If the device 24 orthe system 70 are used for data acquisition no pacing parameters need beset since the device 24 and the system 70 have no pacing capability andno pacing is performed thereby.

It is noted that in accordance with a preferred embodiment of thepresent invention data acquisition may also be performed by implantingthe implantable electrodes 22 in a patient and then operativelyconnecting the implantable leads 22 to the external analyzing unit 64 ofthe system 60 of FIG. 5 or to the external analyzing unit 74 of thesystem 70 of FIG. 6. The pacing parameters of The external analyzingunit 64 of the system 60 are set (including, inter alia, the pacingvoltage, the pacing pulse width, and other relevant pacing parameters),and data collection may be then performed while the patient isrecovering from the electrode implantation procedure for as long as theelectrodes 22 implanted in the patient are connected to the analyzingunit 64. Similarly data may be collected by operatively connecting theimplanted electrodes 22 to the analyzing unit 74 wherein no pacing isperformed.

While the data collected from a patient with an implanted device may bedifferent from data collected from a hospitalized patient using thesystems 60 and 70, the cardiac conditions of the patient may be alteredby instructing the patient to perform certain types of physical activitywhile he is in bed.

For the sake of simplicity, the following description of the dataacquisition method relates to freely moving patients having an implantedpacemaker/ETC device such as the device 21 of FIG. 3A. However, it willbe appreciated that the methods are also adaptable to patients in whichthe device 24 or one of the systems 60 and 70 is used, by suitablyadapting and modifying the methods to the different patient conditionsor to the absence of cardiac pacing when the device 24 or the system 70are used.

Data acquisition

After implantation of the pacemaker/ETC device 21 in the patient, thepatient is sent home for a time period which is estimated as sufficientfor collecting enough data such as a few days or weeks. The patient isinstructed to carry out daily routine behavior. The pacemaker/ETC device21 records data as is disclosed in detail hereinafter. The data is thenoffloaded from the pacemaker/ETC device 21 telemetrically as disclosedhereinabove. The off-loaded data is then stored for further processingby the analyzing unit 23 of FIG. 3A.

Record data structure

Reference is now made to FIG. 7 which is a schematic diagramillustrating the structure of a typical data collection time intervaluseful in the acquisition of data histograms, in accordance with apreferred embodiment of the present invention.

For each cardiac beat, Detected LV event data is collected within theduration of a data collection time interval 71. The data collection timeinterval 71 begins at a starting time point T_(S) and ends at an endingtime point T_(E).

In ETC devices having pacing capability such as the pacemaker/ETC device21 of FIG. 3B, the analyzing unit 64 of the system 60 of FIG. 5 and thelike, the initiation of the data collection time interval 71 istriggered by the detection of an RV event or by the delivering of apacing pulse to the RV. However, in embodiments of the present inventionin which no sensing and no pacing are performed in the RV, theinitiation of the data collection time interval 71 is triggered by thedetection of an RA event or by the delivering of a pacing pulse to theRA.

In ETC devices having no pacing capability such as the pacemaker/ETCdevice 24 of FIG. 4, the analyzing unit 74 of the system 70 of FIG. 6and the like, the initiation of the data collection time interval 71 istriggered by the detection of an RV event. However, in embodiments ofthe present invention in which no sensing is performed in the RV, theinitiation of the data collection time interval 71 is triggered by thedetection of an RA event.

The duration of the time interval 71 is preset by the user orcardiologist before the beginning of the data collection period and doesnot change during the data collection. The duration of the time interval71 is typically 100-150 milliseconds, however, other duration values ofthe data collection time interval 71 may be used. The duration of thedata collection time interval 71 is set such that it is large enough toinclude the LV sensed events representing the myocardial depolarizationwave under extreme cardiac conditions which may be encountered in apatient including, inter alia, various ranges of heart rates with orwithout ETC signal application, with or without pacing in bothnon-treated and drug treated patients. The duration of the datacollection time interval 71 is selected such that it does not extendinto the next heart beat cycle. Practically, the duration of the datacollection time interval 71 may also be limited by the data storagecapacity available in the memory unit of the pacemaker/ETC devices orthe ETC devices disclosed in detail hereinabove.

The data collection time interval 71 is divided into N contiguous timebins 72 of equal duration. The double headed arrow 74 represents theduration of each of the time bins 72 (which is equal to T_(E)−T_(S)).This set of time bins forms the basis for recording a plurality ofhistogram data sets. Each of the plurality of histogram data sets may bestored in the memory unit 44 of the pacemaker/ETC device 21 (FIG. 3B) orof the ETC device 24 (FIG. 4) or in the memory unit 66 of the analyzingunit 64 of the system 60 (FIG. 5) or of the analyzing unit 74 of thesystem 70 (FIG. 6). Each histogram data set of the plurality ofhistogram data sets represents a cumulative time distribution histogramand includes a set of integer variables each representing the cumulativenumber of locally sensed LV events which were detected within aparticular time bin of the N time bins 72 in a plurality of beat cyclesbelonging to a particular histogram data set. Each of the histogramsrepresents data collected from a plurality of beat cycles having incommon a unique set of conditions including a specific LV detectionsensitivity level, the beat being paced or sensed beats, and the beatshaving been collected during a time period in which ETC signal deliverysubstantially affects myocardial depolarization wave conduction velocityor during a time period in which no ETC signal delivery occurred or theETC delivery which did occur did not substantially affect the myocardialdepolarization wave conduction velocity, and having a cycle lengthbelonging to a particular class of cycle lengths as is disclosed indetail hereinbelow. Each particular cycle length class includes heartbeats having a duration falling within predetermined range of cyclelength durations.

Reference is now made to FIG. 8A which is a schematic diagramillustrating the general steps of a method for collecting time histogramdata sets under various cardiac conditions and for determining one ormore sets of alert window parameters and one or more detection parametersets from the histogram data, in accordance with a preferred embodimentof the present invention.

The method includes the implanting of a data collecting device in apatient (step 76). The term data collection device of step 76 is usedherein as a broad term describing a device capable of sensing anddetecting depolarization events in at least two cardiac sites and ofprocessing and storing data. The data collection device is capable ofdelivering ETC non-excitatory signals to the heart. Preferably (but notnecessarily), the device may also be capable of pacing the heart as isknown in the art. For example, The data collection device may includethe implantable electrodes 22 operatively connected to the pacemaker/ETCdevice 21 of FIG. 3A or to the device 24 of FIG. 4. Alternatively, thedata collection device may include the implanted leads 22 operativelyconnected to the external analyzing unit 64 of the system 60 of FIG. 5or to the external analyzing unit 74 of the system 70 of FIG. 6.

The method further includes obtaining the histogram data sets disclosedin detail hereinabove (step 78). The histogram data sets are obtained byusing a plurality of different detection parameters or a plurality ofdifferent detection parameter sets depending, inter alia, on the typeand complexity of the event detection method which is implemented by thedata collection device. Different histogram data sets are obtained underdifferent cardiac conditions such as, but not limited to, differentheart rate ranges, artificially paced heart beats, and naturallyoccurring heart beats (sensed), artificially paced heart beats in thepresence of on-going delivery of non-excitatory ETC signals andnaturally occurring heart beats in the presence of the on-going deliveryof non-excitatory ETC signals. These different conditions are disclosedin detail hereinafter.

The histogram data sets collected by the pacemaker/ETC device 21 may bestored in the memory unit 44 and telemetrically transmitted to theanalyzing unit 23 (FIG. 3A) for processing. If the ETC device 24 of FIG.4 is used for data collecting, the histogram data sets are stored in thememory unit 44 of the device 24. If the system 60 of FIG. 5 is used fordata collection, the histogram data sets collected by the analyzing unit64 are stored in the memory unit 66 for further processing. If thesystem 70 of FIG. 6 is used for data collection, the histogram data setscollected by the analyzing unit 74 are stored in the memory unit 66 forfurther processing.

The method further includes processing of the histogram data setsobtained in step 78 to determine one or more sets of alert windowparameters, and one or more sets of detection parameters (step 80).Typically, each of the alert window parameter sets includes an alertwindow starting time value and an alert window ending time value. Eachof the determined alert window parameter sets and detection parametersets may be suitable for use under a particular combination of cardiacconditions such as a particular heart rate in a sensed or in a pacedheart beat, and in the absence or presence of on-going delivery ofnon-excitatory ETC signals. Each particular set of alert windowparameters may be associated with a particular set of detectionparameters. However, in some cases a common single set of detectionparameters may be associated with some or with all of the sets of alertwindow parameters.

In other cases, a single common set of window parameters may be used forsome or for all of the cardiac conditions disclosed hereinabove.

The method also includes the step of programming an implanted ETC deviceor ETC/pacemaker device with the determined set or sets of alert windowparameters and with the determined set or sets of detection parameters(step 82).

It is noted that, the step 78 and the step 80 may or may not beperformed by the same device. For example, in accordance with apreferred embodiment of the present invention, step 78 may be performedby an implanted device such as but not limited to the device 21 of FIG.3A (or the implanted device 24 of FIG. 4), the stored data may then betelemetrically transmitted to an external analyzing unit such as but notlimited to the analyzing unit 23 of FIG. 3A, step 80 is then performedby the analyzing unit 23 and in step 82 the implanted device 21 of FIG.3A (or the implanted device 24, of FIG. 4) is telemetrically programmedwith the determined set or sets of alert window parameters and with theset or sets of detection parameters.

In accordance with another preferred embodiment of the presentinvention, step 78 may be performed by a device including implantedelectrodes such as the implantable electrodes 22 which are operativelyconnected to an external device such as but not limited to the analyzingunit 64 of FIG. 5 (or the analyzing unit 74 of FIG. 6) and the data isstored in the memory unit 66 of the analyzing unit 64 (or of theanalyzing unit 74). Step 80 is then performed by the analyzing unit 64(or the analyzing unit 74). The implantable electrodes 22 are thendisconnected from the analyzing unit 64 (or from the analyzing unit 74)and in step 82 an implantable ETC or ETC/pacemaker device such as butnot limited to the device 21 of FIG. 3A (or the device 24 of FIG. 4) isconnected to the implantable electrodes 22 and implanted in the patient.The programming (step 82) of the device 21 (or the device 24) with thealert window parameter set of the or sets and with the detectionparameter set(s) may be performed prior to the implantation of thedevice 21 (or the device 24) within the patient or may be performedtelemetrically after implantation of the device 21 (or the device 24).

Reference is now made to FIGS. 8B and 8C which are schematic flowcontrol diagrams illustrating the steps of a data collection method forcollecting time histogram data sets in detail, in accordance with apreferred embodiment of the present invention.

The data collection program embedded within the pacemaker/ETC device 21or the analyzing unit 64 starts by checking whether the user or operatorhas terminated the collection of data (step 90). The user (typically thecardiologist) may terminate data collection by a suitable command whichis transmitted telemetrically to the pacemaker/ETC device 21 of thesystem 20, or input manually to the analyzing unit 64 of the system 60through one of the user interface device(s) 69. Typically, the commandmay set a suitable flag or change the value of a variable which ischecked by the program. However, other suitable methods for terminatingdata collection may be used. If the user did terminate data collectionthe data collection program ends (step 92). If the user did notterminate data collection, the program gets the current sensitivitylevel value SL (step 94). The sensitivity level variable SL may be aninteger variable which can take any integer value selected from a groupof integer numbers, each representing a particular sensitivity valueavailable for use in the pacemaker/ETC device 21 or the analyzing 64.For example, if the event detection sensitivity is determined by thecrossing of a single voltage threshold and the pacemaker/ETC device canhave 8 different sensitivity levels, SL may be any integer in the range1-8.

The data collection program checks whether the pacemaker paced (step96). This is performed by checking the pacing data for the current beatcycle which is stored by the pacemaker/ETC device 21 or by the pacingprogram operating the processing unit 61 of the analyzing unit 64. Ifthe pacemaker paced the data collection program sets the value of thelogical parameter to EV=PACE to indicate a paced beat cycle (step 97)and transfers control to step 100. If the pacemaker did not pace, thedata collection program checks whether the pacemaker sensed (step 98)this is performed by checking the event sensing status data which isstored for the current beat cycle by the pacemaker/ETC device 21 or bythe pacing program operating the processing unit 61 of the analyzingunit 64. If the pacemaker sensed, the data collection program sets thevalue of the logical parameter to EV=SENSE to indicate a sensed beatcycle (step 99) and transfers control to step 100.

The data collection program then checks whether a premature ventricularcontraction (PVC) was detected (step 100). The detection of a PVC isperformed by the pacemaker/ETC device 21 or by the pacing programoperating the processing unit 61 of the analyzing unit 64. A PVC may bedetected using the signals sensed in the RV. As is known in the art,PVC's may be identified by detecting two consecutive ventricular eventswithout an atrial event therebetween. For example, PVC detection methodsused in pacemakers operating in a DDD mode are suitable for use in thedata collection method of the present invention. However, other methodssuitable for PVC detection may be used. PVC detection methods are wellknown in the art, are not the subject matter of the present inventionand will therefore not be discussed in detail hereinafter.

If a PVC was detected the data collection program returns control tostep 90 for avoiding collection of data for the current beat cycle. If aPVC was not detected, the data collection program gets the value of thevariable ETC (step 101). The variable ETC is a logical variable whichcan have the values “ON” and “OFF”. When ETC=OFF the histogram isassumed to represent data considered to be collected under conditions inwhich there was no practical influence of the prior delivery of ETCsignals on the cardiac conduction velocity. When ETC=ON the histogram isassumed to represent data considered to be collected under conditions inwhich the delivery of ETC signals has some influence on the cardiacconduction velocity. The detailed procedure of setting the value of thevariable ETC and the criteria used to set the value of the variable ETCare disclosed in detail hereinafter.

The program then determines the cycle length category CL (step 102). CLis a variable representing the cycle length category which holds aninteger number in the range 1−CLENGTH, where CLENGTH is the number ofcycle length categories.

The cycle length category is determined (step not shown) from the timeinterval between the current RV event detection and the previous RVevent detection. This time interval is known in the art as the “R—Rinterval”. The time of occurrence of detection of the current andprevious RV events are stored in the memory of the pacemakers ETC device21 of FIG. 3A or of the analyzing unit 64 of FIG. 5 as is known in theart.

The CL value of the current R—R interval is determined (steps not shown)by assigning the appropriate cycle length category CL depending on thecurrent value of the R—R interval. The number of cycle length categoriesand the range of R—R interval lengths included in each of the cyclelength categories are predetermined. For example, all R—R intervalshaving a value between 400 milliseconds and 449 milliseconds areassigned a first cycle length category variable value CL=1, all R—Rintervals having a value between 450 milliseconds and 499 millisecondsare assigned a second cycle length category variable value CL=2, all R—Rintervals having a value between 500 milliseconds and 549 millisecondsare assigned a third cycle length category variable value CL=3 and soforth.

It is noted that the above disclosed values of the ranges of the R—Rintervals and CL values are given by way of example only and that thenumber of predetermined cycle length categories values CL which areselected and the selected ranges of the R—R intervals may be varieddepending, inter alia, on the amount of memory available for datastorage, the desired temporal resolution, the processing power of theprocessing unit 30 (FIG. 3A) or of the controller 40 (FIG. 4) and otherpractical considerations.

The program then selects a histogram to be updated HIST(EV,CL,SL,ETC)based on the current values of the variables EV,CL, SL and ETC andupdates the number of beats contributing to the data accumulated in theselected histogram by increasing by one the value of a histogram beatcounter HC(EV,CL,SL,ETC) associated with the selected histogramHIST(EV,CL,SL,ETC) (step 105). It is noted that, the value of all theplurality of histogram beat counters HC(EV,CL,SL,ETC) is set to zero atthe start of the data collection procedure (step not shown). The programthen sets the value of the variable TIME to zero (step 106) and starts atimer (step 108) which updates the value of the variable TIMErepresenting the time from starting of the current RV event detection.The program then checks whether a threshold crossing has occurred (step110). If a threshold crossing does not occur, the program checks whetherthe value of the variable TIME is equal to or larger than the value ofthe variable MAXDELAY (step 112) wherein MAXDELAY is a constant valuerepresenting the longest delay between a detected RV event and adetected LV event value for which the LV event is registered in ahistogram. The value of MAXDELAY is represented by the data collectiontime interval 71 of FIG. 7, and is equal to the number of bins 72multiplied by the bin duration 74 (FIG. 7).

If the value of the variable TIME is not equal to or larger than thevalue of the variable MAXDELAY, the program returns control to step 110.If the value of the variable TIME is equal to or larger than the valueof the variable MAXDELAY, the program returns control to step 90.

If a threshold crossing occurs, the program calculates BINNUMBER theserial number of the time bin 72 within which the threshold crossingoccurred (step 114). The bin number is calculated by dividing thecurrent value of the variable TIME by the constant BINSIZE representingthe duration of the time bins (BINSIZE is represented as the doubleheaded arrow 74 of FIG. 7) and rounding the result up to the nearestinteger value. The program then increments the event count associatedwith the time bin who's number BINNUMBER was calculated by step 114 byadding one to the value of the variable HIST[EV,CL,SL, ETC](BINNUMBER)(step 116).

The program then stops sensing of the LV sensed signal for a blankingtime period of BLANK_T (step 118). The blanking time period BLANK_T isused to prevent spurious event detection caused by LV events havingmultiple peaks. The program then checks whether the value of thevariable TIME is larger than the value of the variable MAXDELAY (step120). If the value of the variable TIME is not larger than the value ofthe variable MAXDELAY, the program returns control to step 110. If thevalue of the variable TIME is larger than the value of the variableMAXDELAY, the program returns control to step 90.

As the cycle length of the patient's heart beats varies during the datacollection time period depending on the state of exertion of the patientand since the detection sensitivity level is typically automaticallychanged by the pacemaker/ETC device as is disclosed in detailhereinafter, the different histogram data sets will include at the endof the data collection period the cumulative time distribution histogramdata for each unique data set.

In order to collect enough data histograms in the shorter cycle lengthscategories, the patient may be asked by the cardiologist or physician toengage in physical activity. In the cases where the data is collected bythe implanted pacemaker/ETC device 21 of FIG. 3A, the physician mayinstruct the patient to engage in a suitable physical activity regimenonce a day or at any other suitable frequency. If the data collection isdone using the system 60, the physician or user may stop datacollection, disconnect the leads 22 from the analyzing unit 64 and askthe patient to perform a suitable physical activity or exercise toincrease his heart rate. The physician or user then reconnects the leads22 to the analyzing unit 64 and continues the data collection.

Additionally, in order to get adequate data collection includingsufficient data for both paced and sensed events, the pacemaker A-Vdelay may be changed. For example, when the data is collected by usingthe system 60 of FIG. 5, the A-V delay be changed by a physician duringthe data collection period, by reprogramming the value of the A-V delayusing the user interface device(s) 69. In another example, when the datais collected by using the implanted pacemaker/ETC device 21 of FIG. 3A,once each night (by system clock) the sum of the histogram beat countersHC(EV,CL,SL,ETC) of all sensed histograms HIST(EV,CL,SL, ETC) havingEV=0 is computed to obtain a first sum representing the total number ofsensed beats collected. The sum of the histogram beat counters of allpaced histograms HIST(EV,CL,SL,ETC) having EV=1 is also computed toobtain a second sum representing the total number of paced beatscollected. The ratio of the first sum and the second sum is thencomputed. If the computed ratio is smaller than a pre-selected lowerlimit such as, but not limited to, 1:20 (paced beats: sensed beats), theA-V delay is shortened. A-V delay shortening by approximately 20milliseconds will typically lead to more paced beats. If the computedratio is larger than a pre-selected upper limit such as, but not limitedto 20:1 (paced beats: sensed beats), the A-V delay is lengthened byapproximately 20 milliseconds for obtaining more sensed beats. In orderto restrict the range of possible automatic modification of the A-Vdelay, high and low limits for A-V delay may be set. For example, a lowA-V delay limit of 100 milliseconds and a high A-V delay limit of 300milliseconds may be set but other different limit values may also beused.

Methods for adjusting the A-V delay of a pacemaker are known in the art.For example, U.S. Pat. No. 5,749,906 to Kieval discloses a methodincluding adjustment of the A-V delay to achieve certain pacingconditions.

Alternatively, In cases were it is not possible to automatically adjustthe A-V delay, if after the data was off-loaded, the user or thecardiologist finds that not enough data histograms for paced events wererecorded, the A-V delay value of the pacemaker/ETC device may beshortened to increase the number of paced events and the patient may besent away for an additional data collection period.

It is noted that the value of SL is set by an independent program (notshown). Various methods (not shown) for changing the detectionsensitivity level may be used (not shown). Preferably, the value of SLis set to a number randomly selected from a group of numbersrepresenting the available sensitivity levels of the pacemaker/ETCdevice. Alternatively, pseudo-random selection of the sensitivity levelvalues may be used. Additionally, the method may use various forms ofcycling of the sensitivity level. The rate of changing of thesensitivity level may be constant or variable. For example, the changingof the sensitivity level may be cyclic, pseudo-random or random, as longas data from enough beats is accumulated for each sensitivity level. Therate of change of the sensitivity level may be fixed, may changeaccording to the time of day, or may be relatively rapid, such that datausing the same sensitivity level would be recorded at different hours ondifferent days. The latter rapid sensitivity change method may be usefulin view of the fact that patient's behavior is probably different atdifferent times during the day.

Reference is now made to FIG. 9 which is a schematic graph illustratinga typical cumulative distribution of cardiac cycle length. Thehorizontal axis represents the cycle length in milliseconds and thevertical axis represents the number of occurrences accumulated over thesampling period for a particular cycle length. The curve 121 representsa typical cycle length cumulative distribution curve which is well knownin the art. The data for such a curve may be collected over a samplingperiod of a few hours or a few days. It is noted that, while the overallcumulative distribution of cycle length may be similar to the exemplarycurve 121 of FIG. 9, the longer cycle lengths are more frequent whilesleeping (at night), and shorter cycles will be more frequent duringworking hours.

It is noted that when the pacemaker/ETC device 21 of FIGS. 3 and 4 isused for collecting data, the amount of storage available on the memoryunit 44 may be practically limited due to, inter alia, size, cost andcurrent consumption of avaliable memory units. This memory limitationmay have to be taken into account with respect to the amount ofhistogram data that may be simultaneously stored in the memory 44. Forexample, turning briefly to FIG. 7, each of the bins 72 of the datacollection time interval 71 may be allocated 3 bytes of memory space.The data collection time interval 71 may be divided into 100 bins 72,each of the bins 72 spanning a time interval 74 of 2 milliseconds.Twelve cycle length categories CL are pre-set. Each of the 12 cyclelength categories CL is associated with cycle lengths falling into thetwelve equal duration ranges 999-950 milliseconds, 949-900 milliseconds,. . . , 449-400 milliseconds. If eight different sensitivity levels SLare used and data is collected for paced and for sensed beat cycles andif a histogram header of 3 bytes is included in each histogram, therequired amount of bytes that needs to be allocated for data histogramstorage under such requirements is given by (3×100+3)×12×8×2=58,176bytes. If histogram data is also collected for sensed and paced beatcycles under ETC delivery conditions which are the histograms HIST[EV,CL SL, ETC] having ETC=ON, 116,352 bytes need to be allocated forhistogram data storage.

Memory may be saved by using dynamic memory allocation techniques knownin the art.

It is noted that, the particular cycle beat ranges (cycle lengthcategories) disclosed hereinabove are given by way of example only andother different cycle-length categories having different cycle-lengthranges may be used. Additionally, while the cycle length categoriesdisclosed hereinabove have cycle length ranges of equal size, in otherpreferred embodiments of the present invention the data collectionmethod may also use cycle length categories having non-identical R—Rinterval collection ranges. For example, all R—R intervals having avalue between 400 milliseconds and 449 milliseconds may be assigned afirst cycle length category variable value CL=1, all R—R intervalshaving a value between 450 milliseconds and 549 milliseconds areassigned a second cycle length category variable value CL=2, all R—Rintervals having a value between 550 milliseconds and 669 millisecondsmay be assigned a third cycle length category variable value CL=3 and soforth.

Reference is now made to FIG. 10 which is a schematic diagramillustrating the steps of the method of updating the value of thelogical variable ETC of FIGS. 8B-8C.

The method may be implemented as a software program which is executed inparallel with the program of FIGS. 8B-8C. on the controller unit 40 ofthe pacemaker/ETC device 21 or on the processing unit 61 of theanalyzing unit 64 or on any other suitable processing unit which is usedfor data collection in the present invention.

The program starts by setting the value of the logical variable ETC toETC=OFF (step 130). The program then sets the value of the counterETC_COUNT to zero (step 134). The program then checks whether an ETCsignal was delivered during the current beat cycle (step 138). If an ETCsignal was delivered during the current beat cycle, the program checkswhether ETC_COUNT=ETC_CHANGE (step 142). ETC_CHANGE is a preset integerconstant. The value of ETC_CHANGE is a fixed preset value. Typically,the value of ETC_CHANGE is empirically found and may depend, inter alia,on the intensity, waveform shape, polarity and duration of the deliveredETC stimulation. Typically, the value of ETC_CHANGE may be in the rangeof approximately 2-8, For example, the value of ETC_CHANGE=6 may beused. However, other values of the ETC_CHANGE may be used.

If an ETC signal was not delivered during the current beat cycle, theprogram checks whether ETC_COUNT=0 (step 146).

In step 142, if ETC_COUNT is equal to ETC_CHANGE control is transferredto step 158. If ETC_COUNT is not equal to ETC_CHANGE the programincrements the current value of ETC_COUNT by one (step 150) andtransfers control to step 158.

In step 146, if ETC_COUNT=0, the program transfers control to step 158and if ETC_COUNT is not equal to zero the program decrements the currentvalue of ETC_COUNT by one (step 154) and transfers control to step 158.

In step 158 the program checks whether ETC_COUNT=ETC_CHANGE. IfETC_COUNT=ETC_CHANGE, the program sets the value of the parameter ETC toETC=ON (step 162) and returns control to step 138. If ETC_COUNT is notequal to ETC_CHANGE, the program sets the value of the parameter ETC toETC=OFF (step 166) and returns control to step 138. The program of FIG.10 thus updates the value of the logical parameter ETC for the currentbeat cycle.

It is noted that, the procedure for updating the value of the logicalvariable ETC disclosed hereinabove and illustrated in FIG. 10 isimplemented as a precaution in case the prior application of ETC signalsdoes have an effect on the velocity of propagation of a depolarizationwave in a portion of the myocardium disposed between the electrode 4A inthe RV and the electrode 6A in the LV (or in the portion of themyocardium disposed between the electrode 2A in the RA and the electrode6A in the LV when the sensing is performed by the electrodes 2A and 6A).If the prior application of ETC signals does not have a substantialeffect on the velocity of propagation of the depolarization wave (as hasbeen found in preliminary experimental results in a small number ofhuman patients), the data histograms collected for cardiac conditionsdiffering only in the value of the parameter ETC may be redundant. Forexample, the histogram pairs HIST(EV, CL, ETC=ON) and HIST(EV, CL,ETC=OFF), may be redundant. However, having such redundant histogramsdoes not adversely affect the method of the present invention since insuch a situation the sets of alert time window parameters correspondingwith the histogram pairs have identical or similar values. Thus, thedata set including these pairs of sets of redundant sets of alert timewindow parameters becomes a partially degenerate data set withoutadversely affecting the method of the present invention. When such adegenerate data set is used for setting the beginning time point andending time point of the alert time window, the timing of the alertwindow will be correctly set since all the sets of alert time windowparameters are computed from actual sampled data, irrespective ofwhether one or more of these sets is redundant.

Ensuring acquisition of paced and sensed data

in order to collect data for all sensitivity level values for each cyclelength value of paced and sensed events with and without ETCstimulation, the sensitivity level is automatically changed by thepacemaker/ETC device 21 or by the analyzing unit 64. The order of changemight be cyclic, pseudo-random or random, as long as a sufficient numberof beats is sampled for each sensitivity level. The rate of change ofthe sensitivity level may be fixed, changing relative to the time ofday, or may be changed relatively fast, so that data collected with thesame sensitivity level would be collected at different hours ondifferent days, as the patients' behavior is probably different atdifferent times during the day. While the overall distribution of cyclelength might be similar to FIG. 9, the longer cycle lengths aretypically more frequent while sleeping (at night), and shorter cyclelengths are typically more frequent during working hours. Thus,preferably, the sensitivity level is randomly or pseudo-randomly changedevery beat cycle to prevent biasing of the results due to time of daybias of cycle length.

Data processing and analysis methods

After enough data was collected by the data collection program of FIGS.8B-8C, the data is telemetrically off-loaded from the pacemaker/ETCdevice 21 to the analyzing unit 24 of the system 20 for furtherprocessing. Alternatively, if the system 60 has been used, the data isstored in memory unit 66 and is available for further processing by theprocessing unit 61.

Reference is now made to FIGS. 11A and 11B which are schematic controlflow diagrams of the main program implementing the method for analyzingacquired data histograms, in accordance with a preferred embodiment ofthe present invention.

The main program uses the data histograms collected as disclosed inhereinabove and illustrated in FIGS. 7 and 8 to determine the alertwindow parameters under a variety of different cardiac conditions. Theconditions include paced and sensed events, the absence and in thepresence of ETC signals and a plurality of different cycle lengthranges. The main program determines a set of appropriate alert windowparameters and an appropriate amplifier sensitivity level for each ofthe above conditions.

The main program starts to analyze the collected data histograms forsensed events in the absence of ETC signal delivery by setting the valueof the parameters EV, and ETC as follows EV=SENSE, ETC=OFF (step 170).The program then sets the value of the cycle length category parameterCL to CL=1 (step 172). The program then transfers control to asensitivity level determining procedure for determining the appropriatesensitivity level SL for the particular histogram having CL=1 (step174). The sensitivity level determining procedure is disclosed in detailhereinafter. The program then transfers control to a window positiondetermining procedure for determining the alert window positionparameters GROUPMIN and GROUPMAX for the particular histogram havingCL=1 (step 176). The parameters GROUPMIN and GROUPMAX are defined indetail hereinafter.

The main program then checks whether the current value of the cyclelength category parameter CL is smaller than the number of the cyclelength categories CLENGTH (step 178). For example, the total number ofcycle length categories used in collecting the data may be twelve cyclelength categories as in the non-limiting example given hereinabove(CLENGTH=12) but other values of CLENGTH may be used according to thetotal number of cycle length categories used in collecting the data. IfCLENGTH is greater than CL, the program increments the value of CL by 1(step 180) and returns control to step 174 for determining the alertwindow parameters SL, GROUPMIN and GROUPMAX of the next cycle lengthcategory. If CLENGTH is not greater than CL, the program transferscontrol to step 182.

In step 182, the program proceeds to analyze the collected datahistograms for sensed events in the presence of ETC signal delivery bysetting the value of the parameters EV, and ETC as follows EV=SENSE,ETC=ON. The program then sets the value of the cycle length categoryparameter CL to CL=1 (step 184). The program then transfers control tothe sensitivity level determining procedure for determining theappropriate sensitivity level SL for the particular histogram havingCL=1 (step 186). The program then transfers control to the windowposition determining procedure for determining the alert window positionparameters GROUPMIN and GROUPMAX for the particular histogram havingCL=1 (step 188).

The main program then checks whether the current value of the cyclelength category parameter CL is smaller than the number of the cyclelength categories CLENGTH (step 190). If CLENGTH is greater than CL, theprogram increments the value of CL by 1 (step 192) and returns controlto step 186 for determining the alert window parameters SL, GROUPMIN andGROUPMAX of the next cycle length category. If CLENGTH is not greaterthan CL, the program transfers control to step 194.

In step 194, the program proceeds to analyze the collected datahistograms for paced events in the absence of ETC signal delivery bysetting the value of the parameters EV, and ETC as follows EV=PACE,ETC=OFF. The program then sets the value of the cycle length categoryparameter CL to CL=1 (step 196). The program then transfers control tothe sensitivity level determining procedure for determining theappropriate sensitivity level SL for the particular histogram havingCL=1 (step 198). The program then transfers control to the windowposition determining procedure for determining the alert window positionparameters GROUPMIN and GROUPMAX for the particular histogram havingCL=1 (step 200).

The main program then checks whether the current value of the cyclelength category parameter CL is smaller than the number of the cyclelength categories CLENGTH (step 202). If CLENGTH is greater than CL, theprogram increments the value of CL by 1 (step 204) and returns controlto step 198 for determining the alert window parameters SL, GROUPMIN andGROUPMAX of the next cycle length category. If CLENGTH is not greaterthan CL, the program transfers control to step 206.

In step 206, the program proceeds to analyze the collected datahistograms for paced events in the presence of ETC signal delivery bysetting the value of the parameters EV, and ETC as follows EV=PACE,ETC=ON. The program then sets the value of the cycle length categoryparameter CL to CL=1 (step 208). The program then transfers control tothe sensitivity level determining procedure for determining theappropriate sensitivity level SL for the particular histogram havingCL=1 (step 210). The program then transfers control to the windowposition determining procedure for determining the alert window positionparameters GROUPMIN and GROUPMAX for the particular histogram havingCL=1 (step 212).

The main program then checks whether the current value of the cyclelength category parameter CL is smaller than the number of the cyclelength categories CLENGTH (step 214). If CLENGTH is greater than CL, theprogram increments the value of CL by 1 (step 216) and returns controlto step 210 for determining the alert window parameters SL, GROUPMIN andGROUPMAX of the next cycle length category. If CLENGTH is not greaterthan CL, the program transfers control to the common window parameterdetermining procedure for computing a parameter set suitable for allcycle length categories and all cardiac conditions, based on the SL,GROUPMIN and GROUPMAX values computed for all the various cardiacconditions disclosed hereinabove (step 206).

After successful analysis of the available histogram data is completedby the main program the result may be an array or Look up tableincluding the alert window parameter sets associated with each of thespecific combinations of the parameters EV, CL, and ETC representing allthe various cardiac conditions as disclosed hereinabove. Alternatively,the analysis may result in a single set of alert window parameterscommonly used for all the various cardiac conditions as disclosedhereinabove.

Reference is now made to FIG. 12 which is a schematic flow controldiagram illustrating the steps of the sensitivity level determiningprocedure used in the main program of FIGS. 11A-11B. The sensitivitylevel determining procedure is used for determining the appropriatesensitivity level and the alert window parameters for a particular cyclelength. The data histogram which was acquired using the lowestsensitivity level (the highest threshold for the specific exemplary caseof using a single positive threshold level) is processed first. The sumof detected events recorded in the data histogram is compared to theexpected cumulative number of detected events for the current datahistogram (TOTBEATS). If not enough events were detected, this indicatesthat the sensitivity level was too low (the threshold is too high), andthe data histogram acquired using the next (higher) sensitivity level isprocessed next.

Ideally, only events that are synchronized to the heart activity, namelythe sensing of the ventricle beat in the LV, are supposed to be recordedin the data histograms. However, practically, various types of spuriousevents may be detected and included in the data histogram. Such spurious(“false”) detected events may include electrical depolarization eventsassociated with PVCs and non-random electrical noise peaks which arecyclic or almost cyclic in nature and therefore occur within the alertwindow period triggered by the RV. The spurious detected events may alsoinclude lead movement artifacts which are likely to be synchronized toheart activity, and may therefore appear in a relatively stable positionwithin the data collection time interval 71 of FIG. 7, and electricalArtifacts which are due to skeletal muscle activation which may or maynot be synchronized with the cardiac cycle. Spurious detected events mayalso include polarization artifacts which are electrical noise generatedby the activation of parts of the ventricle different from theventricle's part or site at which the sensing is performed. When theheart is also paced, the spurious events may include pacing artifacts.During data acquisition, the detection time of the LV depolarizationevent may drift within the data collection time interval 71 because thedetection of spurious events in the RV such as electrical noise,depolarization due to PVCs, and the like may lead to prematureinitiation of data acquisition in the data collection time interval 71.

In addition to the recording of spurious (false) events in the datahistograms, It is may also happen that a “true” event is not recorded ina data histogram even though a depolarization wave did occur in the RV,because the depolarization wave was not conducted to the LV.

If enough detected events are recorded in the data histogram, theprocedure attempts to establish the alert window parameters. A suitablewindow may not be found if the sensitivity level was such that not allthe actual events registered, but some noise did register as detectedevents. In such a case, the procedure may get enough events registeredin the histogram, but the events will be spread out among the bins. Inthis case, the procedure will consider a higher sensitivity level. Ifthe procedure succeeds in finding suitable alert window, the sensitivitylevel for the analyzed histogram is recorded, otherwise an appropriateerror message is returned to inform the user of the failure to establishan appropriate alert window for the currently analyzed data histogram.

Thus, preferably, the beginning time point and the ending time point ofthe alert window are determined such that they are optimized for apredetermined level of LV event detection, while reducing theprobability of spurious event detection.

If, for any of the above disclosed reasons, no adequate alert window wasfound (although there where more events recorded than actual beatshappening), the next (higher) sensitivity level is processed. If noappropriate window is found for any of the sensitivity levels (of aparticular combination of values of CL,EV and ETC, an error message isreturned. The steps of the sensitivity level determining procedure aredisclosed in detail hereinbelow.

The sensitivity level determining procedure starts by setting the valueof the sensitivity level SL to SL=1 which is the lowest sensitivitylevel used for the detection (step 250). For example, if the detectionmethod uses only a single positive threshold crossing criterion, thevalue SL=1 represents the highest voltage threshold level which was usedin data collection. Similarly, if the detection method uses anotherdifferent detection criterion or combination criteria SL=1 willrepresent the least sensitive detection criterion level or the leastsensitive combination of detection criteria which in use will lead tothe smallest number of detections, SL=2 will represent the second leastsensitive detection criterion level or the second least sensitivecombination of detection criteria and the last sensitivity level willrepresent the most sensitive detection criterion level.

The procedure then gets the data histogram array HIST(EV,CL,SL,ETC)(step 252). The procedure then computes the value of the variableTOTBEATS for the current histogram HIST(EV,CL,SL,ETC) by multiplying thepreset parameter P by the value of the histogram beat counterHC(EV,CL,SL,ETC) (step 254). The variable TOTBEATS represents theexpected cumulative number of detected events for the current datahistogram HIST(EV,CL,SL,ETC). The value of histogram beat countervariable HC(EV,CL,SL,ETC) is the actual number of beats included in therecorded data histogram HIST(EV,CL,SL,ETC) (see step 105 of FIG. 8C).The parameter P is a preset parameter representing the desired minimumprobability of event detection (assuming no noise is present). Forexample, If the preset desired minimum probability of event detection isP=0.98 and the current histogram HIST(EV,CL,SL,ETC) includes datarecorded from 100,000 heart beats, the computed value isTOTBEATS=0.98×100,000=98,000 detected events.

The procedure then transfers control to a procedure for computing andreturning the value of the variable HIST_SUMBIN (step 256). The steps ofthe procedure for computing the value of the variable HIST_SUMBIN aredisclosed in detail hereinafter (see FIG. 14). Briefly, the variableHIST_SUMBIN represents the total sum of the number of detected eventswhich are recorded in all the bins 72 of the data collection timeinterval 71 (FIG. 7) and which are stored in the current data histogramHIST(EV,CL,SL,ETC). The procedure then checks whether the current valueof HIST_SUMBIN is larger than the value of the parameter TOTBEATS (step258).

If the current value of HIST_SUMBIN is not larger than the value of thecomputed parameter TOTBEATS, indicating that the desired value ofTOTBEATS is not achievable using the current sensitivity level SL, theprocedure increments the value of the parameter SL by 1 (step 260) andtransfers control to step 252. If the current value of HIST_SUMBIN islarger than the value of the computed parameter TOTBEATS, this indicatesthat the desired value of TOTBEATS is achievable using the currentsensitivity level SL, and the procedure transfers control to the windowposition determining procedure (step 262).

The procedure then checks the output returned by the window positiondetermining procedure (step 264). If the window position determiningprocedure returned the value “OUTPUT OK”, the procedure updates thevariable SENS(EV, CL, ETC) which represents the appropriate sensitivitylevel for cycle length category CL, the current event variable EV andthe current excitable tissue control variable ETC, by settingSENS(EV,CL,ETC)=SL (step 266) and returns control to the main program(step 274). If the window position determining procedure did not returnthe value “OUTPUT OK”, the procedure checks whether SL<SLEVELS (step268). If the current sensitivity level value SL is smaller than thenumber of sensitivity levels SLEVELS, the procedure increments the valueof SL by 1 (step 270), and returns control to step 262. If the currentsensitivity level value SL is not smaller than the number of sensitivitylevels SLEVELS, the procedure returns an error message “ERROR IN WINDOWPLACEMENT” (step 272) and returns control to the main program (step274). In such a case the data set is not considered adequate forgenerating a complete set of alert window parameters.

Reference is now made to FIGS. 13A-13C which are schematic flow controldiagrams illustrating the steps of the window position determiningprocedure used in FIGS. 11A, 11B and in FIG. 12.

The window position determining procedure of FIGS. 13A-13C is used todetermine the alert window parameters. The procedure returns for eachhistogram HIST(EV,CL,SL,ETC), a pair of values, representing thestarting (earliest) bin number and the ending (latest) bin number of thealert window appropriate for the current histogram. These pairs ofstarting and ending bin numbers are stored in an array WINDOW(EV,CL,ETC) in which array, for each specific combination of cycle lengthcategory value CL, EV value and ETC value there are stored a pair ofinteger numbers representing the starting bin number and the ending binnumber for the alert window determined based on the analysis of the datahistogram HIST(EV,CL,SL,ETC) having this specific combination CL, EV andETC values.

The window position determining procedure starts by sorting the bins ofthe current histogram HIST(EV,CL,SL,ETC) (step 300). Generally, thenumber of events recorded in the group of bins constituting an alertwindow should be at least TOTBEATS events and the number of bins withinany alert window is limited to MAXWIN bins. The bin sorting step 300 maybe performed by sorting the bins in descending order of bin valuewherein the bin value is the number of events accumulated in aparticular bin. The sorting of step 300 may be accomplished by anysuitable sorting method such as a heap sort, a bubble sort or by anyother suitable sorting method known in the art. Thus, the step 300results in a sorted list of bins. Next, the procedure finds the number Nwhich is the minimum number of bins containing more than TOTBEATS ofrecorded events by going to the N determining procedure and returning avalue for N (step 302).

The procedure then compiles a bin list NLIST including the first N binswithin the current histogram (step 304). The procedure then sorts thelist NLIST by ascending bin number (step 306). The sorting method may besimilar to the sorting method used in step 300 hereinabove except thatthe sorting is performed according to bin number and not according tothe bin value. However, any other suitable sorting method known in theart may be used in step 306.

The procedure then sets the value of an integer group counter m to m=1(step 308) The procedure thus defines first a bin group GROUP(1) of anumber of bin groups GROUP(m). The procedure sets to zero the value ofthe parameter GROUPSIZE(m) which represents the number of bins currentlyincluded in the bin group GROUP(m) (step 309). The procedure stores thevalue of the bin number of the first bin on the list NLIST in thevariable TEMPBIN (step 310). The procedure then adds the bin numberTEMPBIN of the first bin on NLIST as the first bin number of the bingroup GROUP(m) and removes the bin number TEMPBIN from the bin listNLIST (step 312). The procedure then increments the value of theparameter GROUPSIZE(m) by 1 (step 313). The procedure then checkswhether NLIST is empty (step 314). If NLIST is empty, there is only onegroup of bins containing one bin and the procedure updates the parameterGROUPNUMBER representing the current number of groups by settingGROUPNUMBER=m (step 315), and transfers control to the group sortingprocedure of step 330 for group sorting. If NLIST is not empty, theprocedure proceeds by storing the number of the next bin after TEMPBINin the list NLIST in the variable NEXTBIN (step 316). The procedure thenchecks whether the current first bin in the list NLIST is adjacent tothe last bin added to the current bin group GROUP(m), by checkingwhether NEXTBIN=TEMPBIN+1 (step 318). If the value of NEXTBIN is notequal to TEMPBIN+1, this indicates that the bins are not adjacent binsand the procedure opens a new bin group by incrementing the value of thegroup counter m by 1 (step 320), resets the value of GROUPSIZE(m) tozero (step 321), stores the current value of NEXTBIN in TEMPBIN (step322) and returns control to step 312 for generating the next bin group.

If NEXTBIN=TEMPBIN+1, this indicates that the bins are adjacent bins andthe procedure stores the current value of NEXTBIN in TEMPBIN, adds thebin number NEXTBIN to the current bin group GROUP(m) and removes the binnumber NEXTBIN from the list NLIST (step 324). The procedure thenincrements the value of the parameter GROUPSIZE(m) by 1 (step 326) andreturns control to step 314.

In this way, the procedure generates one or more bin groups, each ofthese groups including contiguously adjacent bins, until the list NLISTis empty.

The group sorting procedure of step 330 is disclosed in detailhereinafter (and illustrated in FIG. 16 hereinbelow). Briefly, the totalnumber of events in each bin group is determined and the groups are thensorted by descending total number of group events.

After sorting the bin groups for the current histogram, the procedurebegins processing the bin group having the largest number of recordedevents by setting a group index L to a value of L=1 (step 332). Thegroup index L represents the position of the bin group within the sortedlist NLIST. The procedure then checks whether GROUPSUM(L)≧TOTBEATS,wherein GROUPSUM(L) is the sum of the number of events recorded in allthe bins in bin group GROUP(L), and TOTBEATS is the expected cumulativenumber of detected events for the current data histogramHIST(EV,CL,SL,ETC) (step 334). If GROUPSUM(L) is smaller than TOTBEATS,the procedure gets the values of GROUPMIN and GROUPMAX for GROUP(L)(step 336). These values were found by the group sorting procedure (seeFIG. 16) as is disclosed in detail hereinafter. The procedure thenchecks whether the current group spans the entire histogram length bychecking whether GROUPMIN=1 and GROUPMAX=MAXBINS, wherein MAXBINS is thetotal number of bins in the histogram (step 338). If GROUPMIN=1 andGROUPMAX=MAXBINS, this means that the current group includes all thebins in the entire histogram. However, since in step 334 the proceduredetermined that the total number of events recorded in the bins of thecurrent group is smaller than the expected total number of events forthe entire histogram, a contradiction is indicated and the procedureevokes an error message “NOT OK” (step 340) and returns control to themain program (step 342).

If, in step 338 GROUPMIN is not equal to 1 or GROUPMAX is not equal toMAXBINS, the procedure transfers control to the group enlargingprocedure for enlarging GROUP(L) (step 344) as is disclosed in detailhereinafter (see FIG. 18) and returns control to step 334.

Going back to step 334, if GROUPSUM(L) is equal to or larger thanTOTBEATS, the procedure transfers control to the group shrinkingprocedure for shrinking GROUP(L) (step 346) as is disclosed in detailhereinafter (see FIG. 17). After control is returned by the groupshrinking procedure, the procedure checks whetherGROUPSIZE(L)>MAXWIN(EV,CL,ETC), wherein MAXWIN(EV,CL,ETC) is an array ora look-up table (LUT) including values representing the maximal windowsize (in bins) which is considered to be the maximal acceptable windowsize for a specific combination of values of the parameters CL, EV andETC. Thus, for example, the value stored in the positionMAXWIN(1,PACE,ON) of the array or LUT MAXWIN(EV,CL,ETC) represents themaximal acceptable window size for a paced beat having a cycle lengthfalling in the first cycle length category and having a logical variableETC=ON. In another example, the value stored in the position MAXWIN(3,SENSE, OFF) of the array or LUT MAXWIN(EV, CL, ETC) represents themaximal acceptable window size for a sensed beat having a cycle lengthfalling within the third cycle length category and having a value of thelogical variable ETC=OFF.

The values of stored in the array or LUT MAXWIN(EV, CL, ETC) areempirically found values which are typically preset before the dataprocessing by the main program is begun. These values may be based,inter alia, on clinical results previously obtained in a plurality ofpatients and on considerations involving a compromise between alertwindow size and acceptable spurious noise levels.

It will be appreciated that some of the values stored in the array orLUT MAXWIN(EV,CL,ETC) may be identical. For example, in accordance withone preferred embodiment of the present invention, the valuesrepresenting the maximal acceptable window size for a plurality of cyclelength categories may be the same. Thus, the array or LUT MAXWIN(EV, CL,ETC) may be partially “degenerate”. In accordance with another preferredembodiment of the present embodiment, the array or LUT MAXWIN(EV, CL,ETC) may completely degenerate, in which case it is replaced by a singleconstant MAXWIN representing a maximal window size acceptable under allcardiac conditions and the check performed in step 348 becomes a checkwhether GROUPSIZE(L)>MAXWIN (this step is not actually shown in FIG.13B).

If GROUPSIZE(L)>MAXWIN(EV,CL,ETC), the procedure checks whetherL=GROUPNUMBER (step 350). If L=GROUPNUMBER, this indicates that thereare no more available bin groups left and that the available collecteddata does not allow assigning for the current histogram an alert windowsize which is equal to or smaller than the maximal acceptable windowsize and the procedure returns an error message “not OK” (step 340) andreturns control to the main program (step 342)

If L is not equal to GROUPNUMBER, this indicates that there are bingroups left to be analyzed and the procedure increments the value of Lby 1 (step 352) and returns control to step 334 for further processingof additional bin group data.

Going back to step 348, if GROUPSIZE(L) is equal to or smaller than thecurrent value of MAXWIN(EV,CL,ETC), this indicates that the size of thecurrent group is acceptable as the size of the alert window and theprocedure stores the current values of GROUPMIN and GROUPMAX as theappropriate pair of values representing the starting (earliest) binnumber and the ending (latest) bin number of the alert window,respectively, appropriate for the current histogram in the array WINDOW(EV,CL,ETC) (step 354), the procedure returns an “OK” message (step 356)and transfers control to the procedure or program from which it wasinvoked (step 342).

Reference is now made to FIG. 14, which is a schematic flow diagramrepresenting the steps of a procedure for determining the sum of thenumber of detected events stored in a given data histogram, inaccordance with a preferred embodiment of the present invention.

The procedure starts by setting the value of an integer counter T to T=1(step 360). The counter T represents the number of the current binwithin the current data histogram HIST(EV, CL,SL,ETC). The procedurealso sets the value of an integer bin counter S to S=0 (step 362). Theprocedure then increments the current value stored in the bin counter Sby the number HIST(EV, CL,SL,ETC)(T) representing the number of detectedevents stored in bin T of the current data histogram HIST(EV, CL,SL,ETC)(step 364). The procedure then checks whether T=MAXBINS (step 366),wherein MAXBINS is the total number of bins in the current datahistogram HIST(EV,CL,SL,ETC). If T is not equal to MAXBINS, theprocedure increments the value of T by 1 (step 368) and transferscontrol to step 364. If T=MAXBINS, the procedure stores the currentvalue of S as the value of HIST_SUMBIN (step 370) and returns control tothe sensitivity level determining procedure of FIG. 12.

Reference is now made to FIG. 15 which is a schematic flow controldiagram illustrating the steps of a procedure for determining the valueof the variable N usable in the window position determining procedure ofFIGS. 13A-13C, in accordance with a preferred embodiment of the presentinvention.

The procedure of FIG. 15 starts setting the value of an integer counterT to T=1 (step 372). The counter T represents the number of the currentbin within the current data histogram HIST(EV, CL,SL,ETC). The procedurealso sets the value of an integer bin counter S to S=0 (step 374). Theprocedure then increments the current value stored in the bin counter Sby the number HIST(EV, CL,SL,ETC)(T) representing the number of detectedevents stored in bin T of the current data histogram HIST(EV, CL,SL,ETC)(step 376). The procedure then checks whether S≧TOTBEATS (Step 378). IfS is not larger than or equal to TOTBEATS the procedure increments thevalue of T by 1 (step 380) and transfers control to step 376. If S islarger than or equal to TOTBEATS the procedure stores the current valueof T as the value of N (step 382) and returns control to the windowposition determining procedure of FIGS. 13A-13C.

Reference is now made to FIG. 16 which is a schematic flow controldiagram illustrating the steps of the group sorting procedure usable inthe window position determining procedure of FIG. 13B, in accordancewith a preferred embodiment of the present invention.

Briefly, the group sorting procedure sorts the groups obtained for thecurrent data histogram by computing the total number of detected eventsstored in all the bins included within each of the groups of the currentdata histogram group GROUP(T), stores the obtained group event sums inan array GROUPSUM(T) and then sorts the groups by sorting the valueswithin the array GROUPSUM(T) by descending order of total group eventnumber.

The procedure sets the value the value of an integer group counter T toT=1 (step 390). The group counter T represents the number of the currentbin group GROUP(T). The procedure also sets the value of an integergroup event counter S to S=0 (step 392). The procedure stores in aninteger variable M the value of the variable GROUPMIN representing theminimal bin number included in the current T′th group GROUP(T), storesin the pointer TEMPBIN the number of detected events which is stored inthe first bin of the current bin group GROUP(T), and stores in aninteger variable L the value of the variable GROUPMAX representing themaximal bin number included in the current T′th group GROUP(T) (step394). The group sorting procedure then updates the value of the groupevent counter S by adding the current value of TEMPBIN to S (step 396).The procedure then checks whether M=L (step 398). If M is not equal toL, indicating that there are additional bins within the current groupGROUP(T), the procedure increments the value of M by 1 and stores thenumber of events stored in the M′th bin of GROUP(T) in TEMPBIN (step400), and transfers control to step 396.

If M is equal to L, indicating that there are no remaining bins withinthe current group GROUP(T), the procedure stores the current value ofgroup event counter S in the variable GROUPSUM(T) representing the totalsum of the events detected in all the bins included in the current groupGROUP(T) (step 402). The procedure then checks whether T=GROUPNUMBER(step 404). If the group counter T is not equal to GROUPNUMBER,indicating that not all the groups for the current data histogram havebeen processed, the procedure increments the value of the group counterT by 1 (step 406) and transfers control to step 392 for further groupprocessing. If T=GROUPNUMBER, indicating that all the groups obtainedfor the current data histogram have been processed, the procedure sortsthe values stored in the array GROUPSUM(T), in descending order(step408) and returns control to the window position determining procedure(of FIG. 13B).

Reference is now made to FIG. 17 which is a schematic flow controldiagram illustrating the steps of the group enlarging procedure usablein the window position determining procedure of FIG. 13B, in accordancewith a preferred embodiment of the present invention. As disclosedhereinabove (in step 334, 336 and 338 of FIG. 13B), the group enlargingprocedure is used to enlarge a bin group in cases in which the currentgroup includes less than TOTBEATS detected events. The current bin groupis enlarged by consecutively adding bins to the group for increasing thetotal number of detected events included in the current bin group.

The group enlarging procedure of FIG. 17 starts by checking whetherGROUPMIN=1 (step 420). If GROUPMIN=1, indicating that the first bin inthe current group is identical to the first bin of the current datahistogram, the procedure transfers control to step 428. If GROUPMIN isnot equal to 1, indicating that the first bin in the current group isnot identical to the first bin of the current data histogram, theprocedure checks whether GROUPMAX=MAXBINS (step 422). IfGROUPMAX=MAXBINS, the procedure decrements the value of GROUPMIN by 1 toadd an additional bin to the group and updates the value of GROUPSUM(L)by adding to it the number of detected events BIN(GROUPMIN) stored inthe bin which was added to the group (step 424). The procedure thenreturns control to the window position determining procedure of FIG.13B.

If GROUPMAX is not equal to MAXBINS, the procedure checks whetherBIN(GROUPMAX+1)≧BIN(GROUPMIN−1) (step 426), wherein BIN(GROUPMAX+1)represents the number of detected events stored in the bin of thecurrent data histogram which is adjacent to the last bin of the currentbin group and which is not included in the current bin group, andBIN(GROUPMAX−1) represents the number of detected events stored in thebin of the current data histogram which is adjacent to the first bin ofthe current bin group and which is not included in the current bingroup. The check of step 426 is performed in order to determine on whichside of the current group the next bin is to be added to the group basedupon a comparison of the number of detected events stored in the twobins which are adjacent to the current first and last bins of thecurrent group.

If BIN(GROUPMAX+1) is not equal to or larger than BIN(GROUPMIN−1), theprocedure transfers control to step 424.

If BIN(GROUPMAX+1)≧BIN(GROUPMIN−1), the procedure increments the valueof GROUPMAX by 1 to add an additional bin to the group and updates thevalue of GROUPSUM(L) by adding to it the number of detected eventsBIN(GROUPMAX) stored in the bin which was added to the group (step 428)and returns control to the window position determining procedure of FIG.13B.

Reference is now made to FIG. 18 which is a schematic flow controldiagram illustrating the steps of the group shrinking procedure usablein the window position determining procedure of FIG. 13B, in accordancewith a preferred embodiment of the present invention. The groupshrinking procedure is invoked by step 334 of the window positiondetermining procedure disclosed hereinabove (FIG. 13B) in cases in whichthe number of events in the current bin group is equal to or larger thanTOTBEATS. The purpose of the group shrinking procedure is to remove fromthe current bin group bins in which the number of detected events iszero, the removal is performed starting from the bins positioned at theedges of the bin group and proceeds until a bin with a non-zero numberof detected events is encountered.

The group shrinking procedure starts by checking whether the number ofdetected events BIN(GROUPMIN) which is stored in the current first binof the current bin group is equal to zero (step 440). IfBIN(GROUPMIN)=0, the procedure removes the “empty” bin from the group byincrementing the value of the first bin number GROUPMIN by 1 (step 442)and returns control to step 440 for checking the next bin. IfBIN(GROUPMIN) is not equal to zero, the bin is not empty and theprocedure transfers control to step 444 for checking the last bin of thegroup. In step 444 the procedure checks whether the number of detectedevents BIN(GROUPMAX) which is stored in the current last bin of thecurrent bin group is equal to zero. If BIN(GROUPMAX)=0, the procedureremoves the empty bin from the group by decrementing the value of thelast bin number GROUPMAX by 1 (step 446) and returns control to step444. If BIN(GROUPMAX) is not equal to zero, the last bin is not empty,the group cannot be further shrunk and the procedure returns control tothe window position determining procedure of FIG. 13B (step 448).

Reference is now made to FIG. 19 which is schematic flow control diagramillustrating the steps of the common window position parametersdetermining procedure usable in the main data analysis program of FIGS.11A-11B, in accordance with a preferred embodiment of the presentinvention. The purpose of the procedure illustrated in FIG. 19 is toanalyze the values of the first and last window bin numbers which werecomputed from all the data histograms as disclosed hereinabove and whichare stored in the array WINDOW(EV,CL,ETC) and to determine therefrom aset of parameters which may be stored in the memory of the ETC andpacemaker/ETC devices of the present invention and used for real timedetermination of the alert window timing parameters. The parametersdetermined by the procedure of FIG. 19 may represent the starting binnumber and the ending bin number of a single fixed alert window alsoreferred to as “static alert window” which will be used for all beatsirrespective of the beat cycle length. This single set of static alertwindow parameters will be used for sensed beats (naturally occuringbeats) and for paced beats, in the presence and in the absence of thedelivery of ETC signals. The details of the use of a static alert windoware disclosed in detail in U.S. patent application to Mika et al., Ser.No. 09/276,460, Titled “APPARATUS AND METHOD FOR TIMING THE DELIVERY OFNON-EXCITATORY ETC SIGNALS TO A HEART”.

In contrast to using a single set of alert window parameters, thestarting time point and the duration of the alert window may be variedfor beats having different cycle length (different R—R intervals). Themethod of adapting the parameters of the alert window (starting timepoint and ending time point) to the current cardiac conditions isreferred to as the “dynamic alert window” method hereinafter.

The parameters determined by the procedure of FIG. 19 may be a set ofapproximation parameters which are used to compute in real time thealert window parameters. One simple way to determine the beginning andthe ending time points for the alert window based on the current knownvalue of the R—R interval and of the value of the current values of thevariables EV and ETC, as determined in real time, is to determine intowhich cycle length category CL the current R—R interval falls and to usethe determined value of the alert window parameters (the starting andending bin numbers) which are stored in the array WINDOW(EV,CL,ETC) tocompute the starting and ending time points of the alert window based onthe known bin duration. The advantage of such a method is that it issimple to implement. The computing of such an approximation may beadvantageous due to the fact that the data recorded in a data histogramwas actually derived from a plurality of beats having various differentcycle lengths. Thus, while the data within a data histogram is used forcomputing an “average” common set of alert window parameters from allthe beat cycles having a duration falling within the duration limits ofa particular arbitrarily chosen cycle length category, the use of such acommon set of alert window parameters for real time determining of thealert window delay and duration for all the beats falling within thecycle length category may result in non-optimal placement of the alertwindow, particularly for those beats having a cycle length value whichis close to the “ends” of the cycle length category values (these endsare the shortest and longest beat cycle duration values which are stillincluded within a particular cycle length category). This non-optimalalert window placement may be tolerated in cases in which a relativelylarge number of cycle length categories is used for data acquisition.However, in some preferred embodiments of the present invention it maybe impractical or undesirable to use a large number of cycle lengthcategories due to data capacity limitations of the memory of animplanted ETC or ETC/pacemaker device, or due to the need to acquire alarger number of cardiac beats in order to have enough data acquired foreach of the cycle length category leading to an increase in the overalltime period required for patient data acquisition. Therefore, inaccordance with another preferred embodiment of the present invention,the alert window parameters stored in the array WINDOW(EV,CL,ETC) may befurther processed to provide a set of approximation parameters which maybe stored in the ETC or pacemaker/ETC device and used to compute in realtime improved approximated values of the beginning time point and theending time point based on the current value of the R—R interval. Theadvantage of this approximation method is that it provides improvedon-line computed approximations of the alert window beginning and endingtime points while not overly increasing the necessary number of cyclelength categories used for data acquisition, which may also beadvantageous in shortening the time period required for collecting thehistogram data sets from the patient.

The common window position parameters determining procedure of FIG. 19starts by determining the values of the variables MAXWINBEG andMAXWINEND (step 500). As disclosed hereinabove, the array WINDOW(EV,CL,ETC) stores a plurality of pairs of bin numbers. The first numberwithin each pair of bin numbers represents the number of the first bin(the bin at the window's beginning of the alert window determined for aparticular combination of the variables EV,CL,ETC as disclosed in detailhereinabove), and the second number within each pair of bin numbersrepresents the number of the last bin (the bin at the window's end) ofthe same alert window. MAXWINBEG is the difference between the highestfirst bin number and the lowest first bin number of all the first binnumbers of all of the pairs of bin numbers stored in the array WINDOW(EV,CL,ETC). MAXWINBEG Therefore represents the maximal difference (inbins) between all the alert window beginning points included in thearray the WINDOW (EV,CL,ETC).

MAXWINEND is the difference between the highest second bin number andthe lowest second bin number of all the second bin numbers of all of thepairs of bin numbers stored in the array WINDOW (EV,CL,ETC). MAXWINENDTherefore represents the maximal difference (in bins) between all thealert window ending points included in the array the WINDOW (EV,CL,ETC).

Determining the values of MAXWINBEG and MAXWINEND may be performed invarious ways. For example, in accordance with one non-limiting example,this may be performed by sorting the window beginnings (the first binnumbers of all the bin number pairs) by ascending bin number, thentaking the difference between the last and the first bin numbers of thesorted list to obtain MAXWINBEG. Similarly, sorting the window endings(the second bin numbers of all the bin number pairs) by ascending binnumber, then taking the difference between the last and first binnumbers of the sorted list to obtain MAXWINEND.

Alternatively, in accordance with another non-limiting example, one maydefine a minimum beginning variable and a maximum beginning variable,both equal to the first (beginning) bin number of the first pair of binnumbers in WINDOW(CL,EV,ETC), and then running through all the other binnumber pairs, updating the value of the minimum beginning variable andthe maximum beginning variable numbers if needed until all the binnumber pairs in the array WINDOW(CL,EV,ETC) are exhausted. Thedifference between the maximum beginning variable value and the minimumbeginning variable value then gives the value of MAXWINBEG. The value ofMAXWINEND is computed by defining a minimum ending variable and amaximum ending variable both equal to the second (ending) bin number ofthe first pair of bin numbers in WINDOW(CL,EV,ETC), and then runningthrough all the other bin number pairs, updating the value of theminimum ending variable and the maximum ending variable numbers ifneeded until all the bin number pairs in the array WINDOW(CL,EV,ETC) areexhausted. The difference between the maximum ending variable value andthe minimum ending variable value then gives the value of MAXWINEND.

It is noted that the values of MAXWINBEG and MAXWINEND may also bedetermined by any other suitable method or algorithm known in the art.After determining the values of MAXWINBEG and MAXWINEND, The procedurecontinues by comparing the values of MAXWINBEG and MAXWINEND to thevalue of a user determined constant MAXSHIFT which represents themaximal allowable value (in bins) of MAXWINBEG and MAXWINEND (step 502).If MAXWINBEG>MAXSHIFT or MAXWINEND>MAXSHIFT indicating the the maximalallowable value has been exceeded, the procedure sets the value of theflag DFLAG to 1 (step 504), transfers control to a procedure fordetermining real-time window approximation parameters (step 506) andreturns control to the main data analysis program (FIG. 11B). IfMAXWINBEG is not larger than MAXSHIFT and MAXWINEND is not larger thanMAXSHIFT, the procedure, the procedure sets the value of the flag DFLAGto zero (step 508), stores the value of MINBEG and MAXEND as the firstbin number and the last bin number of TOT_WINDOW_(step 510), whereinTOT_WINDOW is an array holding two window parameters representing theoverall (unified) alert window, MINBEG represents the lowest value ofthe first (beginning) bin number of all the pairs of bin numbers storedin the array WINDOW(CL,EV, ETC), and MAXEND represent the highest valueof the second (ending) bin number of all the pairs of bin numbers storedin the array WINDOW(CL,EV, ETC).

The procedure then sets an overall sensitivity level SENS_LEVEL for usein conjunction with the window parameters stored in TOT_WINDOW, byselecting the value of the highest sensitivity level determinedMAX[SENS(CL,EV,ETC)] for any of the analyzed data as the value ofSENS_LEVEL (step 512). For example, this may be accomplished by sortingby ascending or descending order all the sensitivity levelsSENSE(EV,CL,ETC) determined by the sensitivity level determiningprocedure of FIG. 12 procedure during the performance of the main dataanalysis program of FIGS. 11A and 11B, and by setting the last value orthe first value, respectively, in the sorted list of sensitivity levelvalues as the value of SENS_LEVEL. After setting the value ofSENS_LEVEL, the procedure returns control to the main data analysisprogram of FIG. 11B (step 514).

The value of SENS_LEVEL and the array TOT_WINDOW are_latertelemetrically or non-telemetrically programmed into the memory unit(not shown) of the implantable ETC device 19 of FIG. 3A or into thememory unit 44 of the devices 21 or 24 (of FIGS. 3A and 4, respectively)and is used in the operation of the devices 19, 21 and 24 for settingthe beginning and ending points of the alert window and the detectionsensitivity level, respectively, of the devices 19 or 21 or 24 inreal-time as disclosed in detail hereinafter.

It is noted that, the value of MAXSHIFT is entered as input by the user(typically the cardiologist performing the data analysis) during theanalysis, and may be based on the user's judgment of the duration ofallowable common (unified) alert window which will result in the a alertwindow which is large enough to include most of the events which need tobe detected while still being positioned such as not to result inunacceptable levels of detection of spurious events due to electricalnoise (synchronous or non-synchronous with the heart beat), PVCs, andthe like. The user's decision about the appropriate value of MAXSHIFTmay be assisted by visually observing the temporal distribution ofdetected events within the various data histograms which the user maydisplay on the display unit 32 of the analyzing unit 23 of the system 20(FIG. 3A) or of the system 60 (FIG. 5) and the system 70 (FIG. 6). Theentry of the value of MAXSHIFT may be performed through a suitable userinterface such as, but not limited to, one or more of the userinterface(s) 31 of FIG. 3A, or one or more of the user interfacedevice(s) 69 of FIGS. 5 and 6.

Reference is now made to FIG. 20 which is a schematic graph useful forunderstanding a method for computing a set of approximation parametersfor the real time computing of the alert window parameters, inaccordance with a preferred embodiment of the present invention. Thevertical axis represents the cycle length in arbitrary units and thehorizontal axis represents the time measured from the detection of an RVevent (the zero time point of the horizontal axis represents the time ofdetection of an RV event. This zero time point of the horizontal axiscoincides with the time of detection of the RV event 11 of FIG. 2. Thehorizontal lines labeled 521, 522, 523, 524 and 525 schematicallyrepresent five alert windows which were determined by the windowposition determining procedure of FIGS. 13A-13C for the first fivecontiguous cycle length categories selected out of the twelve cyclelength categories of the non-limiting example disclosed hereinabove. Itis noted that, for the sake of clarity of illustration, only these fiveselected alert windows are shown in the graph of FIG. 20 and theremaining other seven alert windows are not shown. It is also notedthat, for the sake of clarity of illustration, the starting and endingpoints of the five alert windows represented by the horizontal lines521, 522, 523, 524 and 525 are given in arbitrary time units from thetime of detection of the RV event 11 and not in bin numbers (as they arestored in the array WINDOW(CL,EV,ETC) disclosed hereinabove). Thus, forexample, the alert window represented by the line 523 begins at the timerepresented by the projection of the beginning point B3 of the line 523on the horizontal time axis and ends at the time represented by theprojection of the ending point E3 of the line 523 on the horizontal timeaxis. Similarly, the alert windows represented by the lines 521, 522,524 and 525 have beginning points B1, B2, B4 and B5 and ending pointsE1, E2, E4 and E5, respectively.

The points P1, P2, P3, P4 and P5 represent the mid points of the cyclelength categories used to determine the alert windows represented by thelines 521, 522, 523, 524 and 525, respectively. For example, themidpoint of a cycle length category (not shown in FIG. 20) includingbeat cycles from 550 to 650 millisecond long will be at 600 millisecondson the vertical axis (point not shown). It is noted that, the graph ofFIG. 20 is given by way of a schematic explanatory example only and doesnot represent actual experimentally derived values.

In accordance with one preferred embodiment of the present invention,the real time determination of the alert window for each beat cycle usesa piecewise linear approximation method. In the graph of FIG. 20 all thebeginning points and ending points of all the determined alert windows(of which only the alert windows represented by the lines 521, 522, 523,524 and 525 are illustrated) are connected by lines. For example, thebeginning points B1 and B2 are connected by the dashed line 528, thebeginning points B2 and B3 are connected by the dashed line 529 thebeginning points B3 and B4 are connected by the dashed line 530, thebeginning points B4 and B5 are connected by the dashed line 532.Similarly, the ending points E1 and E2 are connected by the dashed line534, the ending points E2 and E3 are connected by the dashed line 535,the ending points E3 and E4 are connected by the dashed line 536, theending points E4 and E5 are connected by the dashed line 538. The slopeof each of the lines 528, 529, 530, 532,534,535, 536 and 538 may becomputed from the known values of the beginning points B1,B2, B3, B4 andB5, and the ending points E1, E2, E3, E4 and E5. When it is desired tocompute the approximated beginning point PB and the approximated endingpoint PE of an alert window for a detected event having a measuredinterval value represented by the point PX which lies on the verticalcycle length axis between the cycle length category midpoints P4 and P5,the piecewise linear approximation is used by computing these valuesfrom equations 1 and 2:

PB=B 4+(PX−P 4)*(SLOPE−532)   (1)

PE=E 4+(PX−P 4)*(SLOPE−538)   (2)

wherein (SLOPE−532) is the computed value of the slope of the line 532and (SLOPE−538) is the computed value of the slope of the line 538. Itis noted that the slopes of the lines 532 and 538 may or may not beidentical and their values depend on the particular values of the pointsB4 and E4, and B5 and E5 of the computed alert windows represented bythe lines 524 and 525, respectively. Similarly, The values of the slopesof the lines 528 and 534, 529 and 535, and 530 and 524 depend on theparticular determined values of the beginning and ending points of thecorresponding computed alert windows represented by the lines 521, 522,523, 524 and 525.

Preferably, as disclosed for the R—R interval represented by the pointPX, the procedure for linear piecewise approximation uses the beginningand ending points of the line representing the alert window having anassociated midpoint which has an equal or lower value than the value ofthe R—R interval and the slopes of the lines connecting the beginningand ending points of this line with the beginning and ending points ofthe line representing the alert window directly below it in the graph.However, if the R—R interval has a value smaller than the value of thepoint P1 on the vertical axis, the computation procedure uses the slopesof the lines 528 and 534. If the value of the R—R interval is equal toor larger than the value of the midpoint (not shown in FIG. 20) of thelast cycle length category, the procedure uses for the computation thebeginning and ending points of the last alert window (not shown in FIG.20) and the slopes of the lines connecting the beginning point andending point of the last alert window with the corresponding beginningpoint and ending point of the alert window (not shown) which lies abovethe last alert window in the graph of FIG. 20

It is noted that while the cycle length categories who's midpoints P1,P2, P3, P4 and P5 are shown in FIG. 20 do not span identical timeranges, other embodiments of the present invention may be implemented inwhich some or all of the cycle length categories span identical timeranges.

It is further noted that, for the non-limiting particular example usedin describing the invention, for each acquired data set which isanalyzed one may generate four different graphs, corresponding to thefour possible combinations of the two variables EV and ETC. Thesecombinations are EV=SENSE, ETC=OFF; EV=SENSE, ETC=ON; EV=PACE, ETC=OFF;and EV=PACE, ETC=ON. Each of these four graphs (not shown) includestwelve alert windows determined for the corresponding twelve cyclelength categories of the non-limiting example of the invention disclosedhereinabove. Therefore, if one uses the non-limiting example using 12cycle length categories disclosed hereinabove, the set of approximationparameters which is determined includes for each of the four possiblecombinations of EV and ETC 22 slope values, 12 beginning points and 12ending points. Thus, the full set of approximation parameters includes88 slope values, 48 beginning points and 48 ending points. However, ifanother number of cycle length categories is used in data acquisition,the number of approximation parameters will vary accordingly.

The full set of the approximation parameters is telemetrically ornon-telemetrically programmed into the memory unit (not shown) of theimplantable ETC device 19 of FIG. 3A or into the memory unit 44 of thedevices 21 or 24 (FIGS. 3A and 4, respectively) and is used in theoperation of the devices 19, 21 and 24 for real-time computing of theapproximation of the alert window beginning and ending time points forthe various cycle lengths of detected beats under paced and sensed beatconditions in the absence and presence of the delivery of ETC signals.

Reference is now made to FIG. 21 which is a schematic flow controldiagram illustrating the steps of an exemplary procedure for determiningthe real time window approximation parameters of FIG. 19, in accordancewith one preferred embodiment of the present invention. The procedurestarts by computing the approximation parameters for all the possiblecombinations of the parameters EV and ETC from the data stored in thearray WINDOW(CL,EV,ETC) and from the known bin size (step 600). Thepossible combinations are EV=SENSE and ETC=OFF; EV=SENSE and ETC=ON;EV=PACE and ETC=OFF; EV=PACE and ETC=ON. The approximation parametersinclude the beginning time points and ending time points for each of thealert windows determined for each cycle length category in each of theabove possible parameter combinations. The approximation parameters alsoinclude the slopes of each of the lines connecting the beginning points(as disclosed hereinabove and illustrated in FIG. 20) and the slopes ofeach of the lines connecting the ending points (as disclosed hereinaboveand illustrated in FIG. 20) for each of the above possible parametercombinations. The procedure then stores the full set of theapproximation parameters in an array or LUT (step 602).

The procedure then determines the maximal sensitivity level values foreach of the four combinations of the parameters EV and ETC and storesthe resulting four maximal sensitivity level values in an array SL_MAX(EV,ETC) (step 604). The determination of the values of the maximalsensitivity depends on the specific detection method which is used fordetecting the LV events and may be performed in any suitable methodknown in the art. For example, in the above disclosed case where asingle positive threshold crossing method is used, one possible way todetermines the maximal sensitivity level values is to sort each of thefour groups SENS(SENSE,CL,OFF), SENS(SENSE,CL,ON), SENS(PACE,CL,OFF) andSENS(PACE,CL,ON) of sensitivity level values stored in the arraySENS(EV, CL,ETC) (see FIG. 12) in ascending order and storing the lastvalue in each of the sorted groups in the appropriate positions in thearray SL_MAX (EV,ETC). The sensitivity level value groupSENS(SENSE,CL,OFF) includes the sensitivity levels determined for allthe data histograms acquired for the parameter combination EV=SENSE andETC=OFF (no pacing and no ETC signal delivery). The sensitivity levelvalue group SENS(SENSE,CL,ON) includes the sensitivity levels determinedfor all the data histograms acquired for the parameter combinationEV=SENSE and ETC=ON (no pacing and with ETC signal delivery). Thesensitivity level value group SENS(PACE,CL,OFF) includes the sensitivitylevels determined for all the data histograms acquired for the parametercombination EV=PACE and ETC=OFF (with pacing and no ETC signaldelivery). The sensitivity level value group SENS(PACE,CL,ON) includesthe sensitivity levels determined for all the data histograms acquiredfor the parameter combination EV=PACE and ETC=ON (with pacing and withETC signal delivery).

In the non-limiting example disclosed hereinabove each of the groups tobe sorted SENS(SENSE,CL,OFF), SENS(SENSE,CL,ON), SENS(PACE,CL,OFF) andSENS(PACE,CL,ON) includes 12 values of determined sensitivity levels. Itwill be appreciated by those skilled in the art that many other ways ofdetermining the maximal sensitivity levels may be used, depending on thetype of event detection method which is used. Thus, the method ofdetermining the maximal sensitivity levels for each of the above fourgroups SENS(SENSE,CL,OFF), SENS(SENSE,CL,ON), SENS(PACE,CL,OFF) andSENS(PACE,CL,ON), may be adapted to the type of event detection methodwhich is used. The array SL_MAX (EV,ETC) is also telemetrically ornon-telemetrically programmed into the memory unit (not shown) of theimplantable ETC device 19 of FIG. 3A or into the memory unit 44 of thedevices 21 or 24 (FIGS. 3A and 4, respectively) and is used in theoperation of the devices 19, 21 and 24 for real-time setting of thedetection sensitivity level of the devices 19, 21 and 24 as is disclosedin detail hereinafter.

Finally, the procedure returns control to the common window positionparameters determining procedure of FIG. 19 (step 606).

The approximation parameter array or LUT, is used for programming of theimplantable ETC device 19 of FIG. 3A or the devices 21 or 24 (FIGS. 3Aand 4, respectively) as disclosed hereinabove. After programming, theapproximation parameters are used for real-time determination of theapproximated alert window beginning and ending points as disclosed indetail hereinabove and illustrated in FIG. 20. For instance, in the caseof the non-limiting example disclosed hereinabove which includes 12cycle length categories in each of the four possible combinations of theparameters EV and ETC, the stored array or LUT includes 88 slope values,48 beginning points and 48 ending points.

Reference is now made to FIG. 22 which is a schematic control flowdiagram illustrating the steps of a method for real time setting of thebeginning and ending time points of an alert window and of the detectionparameters in an ETC device having pacing capabilities, in accordancewith a preferred embodiment of the present invention. The programimplementing the method of FIG. 22 is operative in the devices 19, 21and 24 after they have been programmed with the appropriate data. Thedata includes the value of the flag DFLAG, the array or LUT ofapproximation parameters as disclosed hereinabove and the array ofmaximal sensitivity level values SL_MAX (EV,ETC) The program starts bygetting the current value of the parameter ETC (step 650). During thereal-time operation of the program, the current value of the parameterETC is continuously updated in real-time by the procedure disclosedhereinabove and illustrated in FIG. 10. The program then checks if thepacemaker circuitry sensed an event (step 652). If the pacemaker sensedan event, the program checks if a PVC was detected (step 654). If a PVCwas detected, the program does not allow the delivery of an ETC signalfor the current beat and returns control to step 650. If a PVC was notdetected, the program updates the value of the parameter EV by settingit's value to EV=SENSE (step 656), and checks the value of the flagDFLAG (step 658).

If in step 652, the pacemaker has not sensed, the program checks if thepacemaker has paced (step 660). If the pacemaker paced, the programupdates the value of the parameter EV by setting it's value to EV=PACE(step 662), and transfers control to step 658 for checking the value ofthe flag DFLAG. If the pacemaker did not pace control is returned tostep 652.

In step 658 If DFLAG=1, the program gets the current measured value ofthe R—R interval from the pacemaker circuitry (step 664), selects theappropriate approximation parameters for the current R—R interval byfinding the value of the cycle length category CL within which thecurrent value of the R—R interval falls (the detailed steps of findingthe value of the cycle length category CL are not shown herein as theyare well known in the art) and using the current values of the cardiaccondition defining variables ETC, EV and CL for the selection of theappropriate approximation parameters from the LUT or array (step 666)and computes the current values of the alert window parameters WINBEGrepresenting the approximated beginning time of the alert window andWINEND representing the approximated ending time of the alert window byusing the equations 1 and 2 as disclosed in detail hereinabove andillustrated in FIG. 20 (step 668).

For example, if the R—R interval is equivalent to the value representedby the point PX of FIG. 20, step 666 selects the value of the beginningpoint B4 (FIG. 20), the ending point E4 (FIG. 20) and the slopes of thelines 532 and 538 (FIG. 20) and in step 668 computes PB and PE fromequations 1 and 2, respectively, and set WINBEG=PB and WINEND=PE.

The program then sets the current sensitivity level to be used by thedetection circuitry by using the sensitivity level stored in the arraySL_MAX(EV,ETC) in the array position defined by the current values ofthe parameters EV and ETC (step 670) and returns control to step 650.

If in step 658 the value of the flag DFLAG is not equal to 1, thisindicates that a single pair of values for the alert window beginningtime point and ending time points and a single common sensitivity valuewere selected as adequate for use with all R—R intervals measured inreal-time irrespective of the cycle length category into which themeasured R—R interval fits (as disclosed in detail in steps 502, 508,510 and 512 of FIG. 19). The program then updates the values of theparameters WINBEG and WINEND by using the two values MINBEG and MAXENDstored in the array TOT_WINDOW (see FIG. 19) such that WINBEG=MINBEG andWINEND=MAXEND (step 672), sets the sensitivity level to the value storedin SENS_LEVEL (step 674) and returns control to step 650.

It will be appreciated by those skilled in the art that the preferredembodiment of the program for real-time setting of the alert windowparameters and the detection sensitivity level disclosed hereinabove andillustrated in FIG. 22, is given by way of example only and that manyvariations and modifications thereof are possible which are includedwithin the scope of the present invention. For example, while the steps666 and 668 of the method of FIG. 22 select the proper linear piecewiseapproximation parameters and computes the values of the alert widowbeginning and ending time points WINBEG and WINEND from the selectedlinear piecewise approximation parameters and the measured R—R interval,other methods (not shown) for computing WINBEG and WINEND may also beused based on other approximation methods known in the art such as, butnot limited to, spline approximation methods or the like. Additionally,in accordance with another preferred embodiment of the presentinvention, the steps the steps 666 and 668 of FIG. 22 may be replaced bysteps(not shown) which do not perform an approximation computation butinstead compute the beginning point and ending point of the alert windowdirectly from the beginning bin number and the ending bin number of thearray WINDOW(EV,CL,ETC) and from the known bin size (the bin duration).In this preferred embodiment, the data in the LUT which is stored in thedevice includes the array WINDOW(EV,CL,ETC), the array SL_MAX(EV,ETC),the value of the flag DFLAG and the bin size (in time units). Asdisclosed hereinabove, the latter embodiment may be used in cases wherethe data acquisition was performed using a large number of cycle lengthcategories which may obviate the need for performing the approximation.

It is noted that, while the above disclosed methods and procedures areadapted for devices which include pacing circuitry, Such as theimplantable device 21 of FIG. 3A, the analyzing unit 64 of the system 60of FIG. 5 and the like, the methods of the present invention may also beadapted with some modifications for use with devices having no cardiacpacing capability, such as the device 24 of FIG. 4, the analyzing unit74 of the system 70 of FIG. 6, and the like.

Reference is now made to FIGS. 23A-23B which are schematic flow controldiagrams illustrating the steps of a method for acquiring time histogramdata sets under various cardiac conditions in the absence of artificialcardiac pacing and for determining one or more sets of alert windowparameters or approximation parameters and one or more detectionparameter sets from the histogram data, in accordance with a preferredembodiment of the present invention.

The method illustrated in FIGS. 23A-23B is a modified version of themore general method disclosed hereinabove and illustrated in FIGS.8B-8C. The difference between the two procedures is that in the methodof FIGS. 23A-23B there is no pacing during the data acquisition timeperiod.

The data collection program embedded within the pacemaker/ETC device 24of FIG. 4 or the analyzing unit 74 of FIG. 6 starts by checking whetherthe user or operator has terminated the collection of data (step 690).The user (typically the cardiologist) may terminate data collection by asuitable command which is transmitted telemetrically to thepacemaker/ETC device 24, or input manually to the analyzing unit 74 ofthe system 70 through one of the user interface device(s) 69. Typically,the command may set a suitable flag or change the value of a variablewhich is checked by the program. However, other suitable methods forterminating data collection may be used. If the user did terminate datacollection the data collection program ends (step 692). If the user didnot terminate data collection, the program gets the current sensitivitylevel value SL (step 694). The sensitivity level variable SL may be aninteger variable which can take any integer value selected from a groupof integer numbers, each representing a particular sensitivity valueavailable for use in the pacemaker/ETC device 24 or the analyzing unit74. For example, if the event detection sensitivity is determined by thecrossing of a single voltage threshold and the pacemaker/ETC device canhave 8 different sensitivity levels, SL may be any integer in the range1-8.

The data collection program checks whether the device 24 (or the 74)sensed an event in the RV chamber (step 696). This is performed by theappropriate sensing unit of the sensing units 38 which is operativelyassociated with the sensing electrode (not shown) of the implantableleads 22 which is positioned in the RV. If the device sensed an RVevent, the data collection program sets the value of the logicalparameter to EV=SENSE to indicate a sensed beat cycle (step 699) andchecks whether a premature ventricular contraction (PVC) was detected(step 700). The detection of a PVC is performed by the ETC device 24 orby the pacing program operating the processing unit 61 of the analyzingunit 74.

It is noted that, while the device 24 and the analyzing unit 74 do notinclude pacing circuitry for pacing the heart, they do contain suitablecircuitry (not shown in detail) which is capable of detecting PVCs. APVC may be detected using the signals sensed in the RV. As is known inthe art, PVC's may be identified by detecting two consecutiveventricular events without an atrial event therebetween. For example,the PVC detection methods used in pacemakers operating in a DDD mode aresuitable for use in the data collection method of the present invention.

However, other methods suitable for PVC detection may be used. PVCdetection methods are well known in the art, are not the subject matterof the present invention and will therefore not be discussed in detailhereinafter.

If a PVC was detected the data collection program returns control tostep 690 for avoiding collection of data for the current beat cycle. Ifa PVC was not detected, the data collection program gets the value ofthe variable ETC (step 701). The variable ETC is a logical variablewhich can have the values “ON” and “OFF”. When ETC=OFF the histogramrepresents data considered to be collected under conditions in whichthere was no practically substantial influence of the delivery of ETCsignals on the cardiac conduction velocity. When ETC=ON the histogramrepresents data considered to be collected under conditions in which thedelivery of ETC signals has substantial influence of on the cardiacconduction velocity. The detailed procedure of setting the value of thevariable ETC and the criteria used to set the value of the variable ETCare disclosed in detail hereinabove and illustrated in FIG. 10. Theremaining steps of the data acquisition program of FIGS. 23A-23B aresimilar to the equivalent steps of the data acquisition program of FIGS.8B-8C. Steps 701, 702, 704, 705, 706, 708, 710, 712, 714, 716, 718 and720 of FIGS. 23A-23B are similar to steps 101, 102, 104, 105, 106, 108,110, 112, 114, 116, 118 and 120, respectively, of FIGS. 8B-8C, exceptthat the data histograms HIST(EV,CL,SL,ETC) of the steps of FIGS.23A-23B represent a degenerate set of the data histogramsHIST(EV,CL,SL,ETC) of FIGS. 8B-8C since the value of the parameter EV,as set by step 699 of the method of FIG. 23A, can only be EV=SENSEbecause the device 24 and the analyzing unit 74 have no pacingcapability. Thus, the total number of the data histograms acquired bythe data acquisition method of FIGS. 23A-23B is half of the total numberof the data histograms acquired by the data acquisition method of FIGS.8B-8C.

It is noted that in step 712 of FIG. 23B, if TIME>MAXDELAY, control isreturned to step 690. In step 720 of FIG. 23B, if TIME>MAXDELAY, controlis returned to step 690.

It is further noted that, when the data acquisition is performed by thedevice 24 of FIG. 4 or by the analyzing unit 74 of FIG. 6, using thedata acquisition program illustrated in FIGS. 23A-23B, the program fordetermining the parameters of the alert window in real-time must also bemodified since no pacing is performed by the device 24 or the analyzingunit 74.

Reference is now made to FIG. 24 which is a schematic control flowdiagram illustrating the steps of a method for real time setting of thebeginning and ending time points of an alert window and of the detectionparameters in a non-pacing ETC device, in accordance with anotherpreferred embodiment of the present invention.

The program implementing the method of FIG. 24 is operative in thedevice 24 of FIG. 3A or in the analyzing unit 74 of the system 70 ofFIG. 6 after they have been programmed with the appropriate data. Thedata includes the value of the flag DFLAG, the array or LUT ofapproximation parameters as disclosed hereinabove and the array ofmaximal sensitivity level values SL_MAX (EV,ETC).

It is noted that while the device 24 and the analyzing unit 74 do nothave pacing capability, they include all the necessary circuitry andembedded programs for sensing and detecting events in one or morecardiac chambers as is known in the art and they are capable ofdetermining and storing the R—R interval of the current beat as is knownin the art. If the device 24 is used, the current value of the R—Rinterval is stored in the memory unit 44. If the analyzing unit 74 isused, the current value of the R—R interval is stored in the memory unit66.

The program starts by getting the current value of the parameter ETC(step 850). During the real-time operation of the program, the currentvalue of the parameter ETC is continuously updated in real-time by theprocedure disclosed hereinabove and illustrated in FIG. 10. The programthen checks if the detection circuitry sensed an event in the rightventricle chamber (step 852). When the program is embedded in the device24 of FIG. 4, the sensing is performed by the appropriate sensing unitof the sensing units 38 which is associated with the sensing electrodepositioned in the right ventricle such as the electrode or electrodepair 4A (FIG. 1). When the program is embedded in the analyzing unit 74of FIG. 6, the sensing is performed by the circuitry of the front end 62which is associated with the sensing electrode positioned in the rightventricle such as the electrode or electrode pair 4A (FIG. 1). If anevent was sensed in the right ventricle chamber, the program checks if aPVC was detected (step 854). If a PVC was detected, the program does notallow the delivery of an ETC signal for the current beat and returnscontrol to step 850. If a PVC was not detected, the program updates thevalue of the parameter EV by setting it's value to EV=SENSE (step 856),and checks the value of the flag DFLAG (step 858).

In step 858 If DFLAG=1, the program gets the current measured value ofthe R—R interval from the memory unit 44 of the device 24 or from thememory unit 66 of the analyzing unit 74 (step 864), selects theappropriate approximation parameters for the current R—R interval asdisclosed in detail hereinabove (step 866) for FIG. 22 and computes thecurrent values of the alert window parameters WINBEG representing theapproximated beginning time of the alert window and WINEND representingthe approximated ending time of the alert window by using the equations1 and 2 as disclosed in detail hereinabove and illustrated in FIG. 20(step 868).

The program then sets the current sensitivity level to be used by thedetection circuitry by using the sensitivity level stored in the arraySL_MAX(EV,ETC) in the array position defined by the current value of theparameter ETC (step 870) and returns control to step 650. It is notedthat the array SL_MAX(EV,ETC) as determined by the data acquisitionprogram of FIGS. 23A-23B is a degenerate form of the arraySL_MAX(EV,ETC) determined by the data acquisition program of FIGS. 8B-8Csince the parameter EV can have only the value EV=SENSE, therefore thedegenerate array SL_MAX(EV,ETC) includes only two valid sensitivitylevels for the cases in which ETC=ON and ETC=OFF.

If in step 858 the value of the flag DFLAG is not equal to 1, thisindicates that a single pair of values for the alert window beginningtime point and ending time points and a single common sensitivity valuewere selected as adequate for use with all R—R intervals measured inreal-time irrespective of the cycle length category into which themeasured R—R interval fits (as disclosed in detail in steps 502, 508,510 and 512 of FIG. 19). The program then updates the values of theparameters WINBEG and WINEND by using the two values MINBEG and MAXENDstored in the array TOT_WINDOW (see FIG. 19) such that WINBEG=MINBEG andWINEND=MAXEND (step 872), sets the sensitivity level to the value storedin SENS_LEVEL (step 874) and returns control to step 850.

It is noted that, the program of FIG. 24 may be modified to use variousdifferent approximation methods such as a spline approximation method orother suitable approximation methods for computing the approximatedalert window beginning and ending time points, as disclosed for theprogram of FIG. 22 hereinabove. Additionally, in accordance with anotherpreferred embodiment of the present invention, the steps the steps 866and 868 of FIG. 24 may be replaced by steps (not shown) which do notperform an approximation computation but instead compute the beginningpoint and ending point of the alert window directly from the beginningbin number and the ending bin number of the array WINDOW(EV,CL,ETC) andfrom the known bin size (the bin duration). In this preferredembodiment, the data in the LUT which is stored in the device includesthe array WINDOW(EV,CL,ETC), the array SL_MAX(EV,ETC), the value of theflag DFLAG and the bin size (in time units). As disclosed hereinabove,this embodiment may be used in cases where the data acquisition wasperformed by the program of FIGS. 8B-8C using a large number of cyclelength categories which may obviate the need for performing theapproximation.

It is further noted that all the methods and procedures disclosedhereinabove are adapted for use with devices having detection circuitrywhich is capable of fast switching of the detection sensitivity inreal-time. This means that at least one of the sensing units 38 of thedevices 21 and 24 is capable of controllably switching from onesensitivity level to another sensitivity level within a time periodwhich is short enough to implement sensitivity level changes from oneheart beat to the next heart beat. Similarly, the front end 62 of theanalyzing units 64 and 74 will also be capable of controllable fastswitching between different sensitivity levels. For example, thesensitivity level may be controllably switched by controllably changingthe threshold level of a comparator circuit (not shown). However, othersuitable methods may be used for sensitivity changing. The design andimplementation of such fast circuits for changing detection sensitivitylevels is well known in the art, is not the subject matter of thepresent invention and is therefore not disclosed in detail herein.Moreover, even if the circuitry of a device used for patient datacollection is not fast enough to affect a sensitivity level change on abeat by beat basis, the full set of histogram data may still becollected by acquiring data at a first sensitivity level from a firstgroup of beats, changing the sensitivity level, acquiring data from asecond group of beats and so forth until enough data has been acquiredfor all sensitivity levels.

It is still further noted that, while in the programs disclosedhereinabove and illustrated in FIGS. 22 and 24 the various determinedapproximation parameters are stored in an LUT or array, the variousdetermined sensitivity levels are stored in an array SL_MAX(EV,ETC)and/or a variable SENS_LEVEL, and DFLAG may be stored in the LUT orseparately, the way of storing the approximation parameters, thesensitivity levels and the value of DFLAG is not critical to theinvention and many different ways of organizing and storing thisinformation may be implemented as is well known in the art.

It is yet further noted that, while the present invention is disclosedas adapted for use in the ETC devices and in ETC/pacemaker devicesdisclosed hereinabove, the methods of the present invention may also beadapted for use in devices having additional capabilities. For example,in accordance with another preferred embodiment of the presentinvention, devices may be implemented which include in addition to thepacing capabilities and the ETC signal delivering capabilities, thecapability to deliver defibrilation pulses to the heart as is well knownin the art.

Furthermore, while the programs and procedures disclosed hereinabove areadapted for use with an exemplary embodiment of the present inventionwhich uses the R—R interval computed from events sensed in or about theright ventricle, other preferred embodiments of the present inventionmay be adapted for using an A—A interval which is the computed timeinterval between consecutive detected atrial events which are locallysensed in or about the right atrium. The electrode configurations forsuch a preferred embodiment are disclosed in detail in the abovereferenced co-pending U.S. patent application to Mika et al., Ser. No.09/276,460.

Further yet, for each beat cycle, after the beginning and ending timepoints of the dynamic alert window and the detection sensitivity levelhave been determined as disclosed hereinabove, if an ETC non-excitatorysignal is delivered to the heart, the delivery may be performed asdisclosed in detail hereinabove (FIG. 2) or as disclosed in the abovereferenced U.S. patent application Ser. No. 09/276,460. Thus, variouspreferred embodiments of the present invention make use of the delayperiod ΔT4 of FIG. 2 and may or may not make use of the refractoryperiod ΔT1, the inhibition window ΔTI, and the alert refractory periodΔT7 of FIG. 2. Some modifications of the method illustrated in FIG. 2may need to be implemented. For example, since the starting and endingpoints of the alert window of the present invention are dynamically setfor each beat, the inhibition window ΔTI may be dynamically set for eachbeat based on the time T₀ of detection of the RV event (or alternativelythe RA event if detection in the right atrium is used) of the currentcardiac beat and on the value of the starting time point T₁ of the alertwindow ΔT3 dynamically computed for the current cardiac beat. Anothermodification that may be implemented is that the duration of the alertrefractory period ΔT7 may be set such that the inequalityΔT7>ΔT3+ΔT4+ΔT5 _(MAX) disclosed hereinabove holds for all possiblevalues of ΔT3. This means that the duration of ΔT7 is set using thehighest possible duration of the alert window which may be set under anyof the various cardiac conditions (including the use of theapproximation method disclosed hereinabove if applied). Thus, the valueof ΔT7 may be set to satisfy the above inequality based on the maximalduration of the alert window time period computable from the LUT orarray holding the alert window parameters as determined from the datacollected in the data collection session disclosed hereinabove.

In accordance with still another preferred embodiment of the presentinvention, the ETC device and the ETC/pacemaker device may also havefencing capabilities as disclosed in detail in PCT Application,International Publication Number WO 98/10830, titled “FENCING OF CARDIACMUSCLES” to Ben Haim et al.

It is noted that throughout the present application the term “real-time”is used broadly to imply on-line performance of determinations,computations and approximations which are performed on the fly by thedevices of the present invention for each cardiac beat cycle.

It is further noted that in the preferred embodiments of the inventiondisclosed hereinabove and illustrated in FIGS. 22 and 24 the value ofthe R—R interval which is used for determining the alert windowbeginning and ending time points is the currently measured“instantaneous” time interval between the detection of an RV event inthe previous heart beat and the detection of an RV event in the currentheart beat. However, due to the natural fluctuation of the R—R intervalsit may be desired to use an average R—R interval for the real timecomputation of the alert window beginning and ending time points. Thus,in accordance with another preferred embodiment of the presentinvention, the procedures of FIGS. 22 and 24 may compute the currentvalue of an average R—R interval (the detailed steps of such acomputation of an average interval are well known in the art and aretherefore not shown in FIGS. 22 and 24) and use it for the real-timecomputation of the alert window beginning and ending time points. Forexample, the programs of FIGS. 22 and 24 may store the R—R-intervals ofthe last K consecutive heart beats in a the memory 44 or 66 and computethe average R—R interval by summing these K R—R intervals and dividingthe sum by K for each heart beat. In the next heart beat, the value ofthe currently measured R—R interval is added to the beginning of thelist of K values, the earliest of the stored R—R interval values isremoved from the list and the average is computed again. This may beimplemented using a first in first out (FIFO) buffer or by any othersuitable method for computing a dynamic average known in the art. Whensuch an averaged R—R interval is used for computing the alert windowbeginning and ending time points, the number of stored R—R intervalvalues K is preferably a small number in the range of 2-5 to reduce thepossible effect of masking or attenuating abrupt changes in the R—Rinterval due to the averaging.

Since spurious detection in the RV of signals which are not true RVevents may introduce an error in the calculation of such an average R—Rinterval, it may be desired to use the median of the R—R interval valuesinstead of using their mean. In such preferred embodiments which use acomputed median, the median value may preferably be computed from anumber of stored R—R interval in the range of approximately 5-8 R—Rintervals to reduce errors due to PVCs and the like.

It is noted that, throughout the application, the parameters ETC,EV, andCL, are also commonly referred to as the cardiac condition definingparameters. However, the variables ETC, EV and CL used in FIGS. 22 and24 are generally referred to as the cardiac condition defining variablesas they are updated on-line on a beat by beat basis. Thus, in FIGS. 22and 24, the current values of the cardiac condition defining variablesare used to select the appropriate set of approximation parametershaving a matching set of associated values of cardiac condition definingparameters.

It is further noted that all the devices illustrated in FIGS. 1, 3A, 3B,4, 5 and 6 include one or more power sources (not shown for the sake ofclarity of illustration). The power source(s) of the implantable devicessuch as the device 1 of FIG. 1 and the device 19 of FIG. 3A, the device21 of FIG. 3B and the device 24 of FIG. 4 may be any suitable electricalbattery known in the art. In the devices which are not implanted withinthe body of the patients such as the analyzing units 64 and 74 of FIGS.5 and 6, respectively, the power source may be any suitable power sourceknown in the art such as a mains operated DC power supply, a battery orany other suitable source of electrical power known in the art. Suchpower sources are well known in the art, are not the subject matter ofthe present invention, and are therefore not described in detailhereinabove.

While the invention has been described with respect to a limited numberof embodiments, many variations, modifications and other applications ofthe invention may be made which will be apparent to those skilled in theart. The present invention is thus not to be construed as limited by themodes of operation of the embodiments particularly described but may bepracticed according to its concept, spirit and scope, as may be morereadily understood by consideration of the appended claims.

What is claimed is:
 1. A method for setting the parameters of an alert time window in an excitable tissue control device operative under a plurality of different cardiac conditions of a heart of a patient, the method comprising the steps of: providing said excitable tissue control device with a set of data, said set of data comprises a plurality of sets of alert time window parameters, each set of alert time window parameters of said plurality of sets of alert time window parameters is associated with one of said plurality of different cardiac conditions, each set of alert time window parameters of said plurality of sets of alert time window parameters comprises at least a set of timing parameters usable for obtaining a beginning time point and an ending time point for said alert time window, each set of alert time window parameters of said plurality of sets of alert time window parameters is obtained by processing data collected from a plurality of cardiac beats of said heart of said patient under said plurality of different cardiac conditions within a data collection session prior to said step of providing; automatically selecting, for a current beat cycle of said heart, a current set of alert time window parameters of said plurality of sets of alert time window parameters based on the current cardiac conditions detected for said current beat cycle; using, for said current beat cycle, said current set of alert time window parameters selected in said step of automatically selecting to start and terminate said alert time window based on the time of detecting a first depolarization event at or about a first cardiac site; detecting within the duration of said alert time window of said current beat cycle a second depolarization event at a second cardiac site of said heart; and triggering the delivery of a delayed non-excitatory excitable tissue control signal at or about said second cardiac site based on the time of detection of said second depolarization event.
 2. The method according to claim 1 wherein each set of alert time window parameters of said plurality of sets of alert time window parameters further comprises at least one detection sensitivity parameter having a value representing a detection sensitivity level, and wherein said step of using further includes using said value of said detection sensitivity parameter to set the detection sensitivity level used within the duration of said alert time window of said current beat cycle.
 3. The method according to claim 2 wherein said at least one detection sensitivity parameter comprises a voltage threshold level.
 4. The method according to claim 2 wherein said at least one detection sensitivity parameter comprises at least one morphological detection parameter.
 5. The method according to claim 2 wherein said set of data is a degenerate set of data in which at least some of said sets of alert time window parameters of said plurality of sets of alert time window parameters have identical values of said at least one detection sensitivity parameter.
 6. The method according to claim 1 wherein said plurality of cardiac conditions comprises beats having a plurality of different beat to beat time intervals representing different instantaneous heart rates of said heart.
 7. The method according to claim 1 wherein said plurality of cardiac conditions further comprises beats initiated by the natural pacemaker of said heart and beats initiated by a pacing pulse delivered by said excitable tissue control device.
 8. The method according to claim 1 wherein said plurality of cardiac conditions comprises beats occurring during a time period in which the prior application of excitable tissue control signals results in a change of the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart, and beats occurring during a time period in which the prior application of excitable tissue control signals does not result in a change in the velocity of propagation of a depolarization wave in a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart.
 9. The method according to claim 1 wherein said set of timing parameters of said alert time window parameters comprises a beginning time point value and an ending time point value for said alert time window.
 10. The method according to claim 1 wherein said excitable tissue control device is provided with a value of the bin duration of a time bin used for collecting data within said data collection session, said set of timing parameters of said alert time window parameters comprises a starting bin number and an ending bin number and wherein said step of using includes computing the starting time point and ending time point of said alert time window from said bin duration, said starting bin number and said ending bin number, prior to said starting of said alert time window.
 11. The method according to claim 1 wherein said set of timing parameters comprises a set of approximation parameters and wherein said processing of said step of providing comprises using an approximation method to process said data collected from said heart in said data collection session to obtain a plurality of sets of approximation parameters, usable for computing improved approximated values of the beginning time point and the ending time point of said alert time window.
 12. The method according to claim 11 wherein said approximation method is a linear piecewise approximation method, said set of approximation parameters comprises a beginning time point parameter and a first slope parameter associated with said beginning time point parameter, an ending time point parameter and a second slope parameter associated with said ending time point parameter, and wherein said step of using comprises computing an approximated beginning time point for said alert time window of said current beat cycle from the values of the current cycle length measured for said current beat cycle, said first slope parameter and said beginning time point parameter, and computing an approximated ending time point for said alert time window of said current beat cycle from the values of said current cycle length, said second slope parameter and said ending time point parameter.
 13. The method according to claim 12 wherein said current cycle length is the instantaneous cycle length determined from the current R—R interval or the current A—A interval measured for said current beat cycle.
 14. The method according to claim 12 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive R—R intervals including the R—R interval of said current beat cycle.
 15. The method according to claim 12 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive A—A intervals including the A—A interval of said current beat cycle.
 16. The method according to claim 1 wherein said set of timing parameters comprises said beginning time point and said ending time point of said alert time window.
 17. The method according to claim 1 wherein said set of data is a degenerate set of data in which at least some of said sets of alert time window parameters of said plurality of sets of alert time window parameters have identical values of said set of timing parameters.
 18. The method according to claim 1 wherein said first cardiac site is the right ventricle of said heart and said second cardiac site is the left ventricle of said heart.
 19. The method according to claim 1 wherein said first cardiac site is the right atrium of said heart and said second cardiac site is the left ventricle of said heart.
 20. A method for setting the parameters of an alert time window in an excitable tissue control device operative under a plurality of different cardiac conditions of a heart of a patient, the method comprising the steps of: providing said excitable tissue control device with a set of data, said set of data comprises a plurality of sets of alert time window parameters, each set of alert time window parameters is uniquely associated with a different set of values of a plurality of cardiac condition defining parameters identifying one of said plurality of different cardiac conditions, each set of alert time window parameters of said plurality of sets of alert time window parameters comprises at least a set of timing parameters usable for obtaining a beginning time point and an ending time point for said alert time window, each set of alert time window parameters of said plurality of sets of alert time window parameters is obtained by processing data collected from a plurality of cardiac beats of said heart of said patient under said plurality of different cardiac conditions within a data collection session prior to said step of providing; updating for a current beat cycle of said heart the values of a plurality of cardiac condition defining variables corresponding to said cardiac condition defining parameters; automatically selecting for said current beat cycle a current set of alert time window parameters of said plurality of sets of alert time window parameters based on the current values of said cardiac condition defining variables; using, for said current beat cycle, said current set of alert time window parameters selected in said step of automatically selecting to start and terminate said alert time window based on the time of detecting a first depolarization event at or about a first cardiac site; detecting within the duration of said alert time window of said current beat cycle a second depolarization event at a second cardiac site of said heart; and triggering the delivery of a delayed non-excitatory excitable tissue control signal at or about said second cardiac site based on the time of detection of said second depolarization event.
 21. The method according to claim 20 wherein each set of alert time window parameters of said plurality of sets of alert time window parameters further comprises at least one detection sensitivity parameter having a value representing a detection sensitivity level, and wherein said step of using further includes using said value of said detection sensitivity parameter to set the detection sensitivity level of said excitable tissue control device for said current beat cycle.
 22. The method according to claim 21 wherein said at least one detection sensitivity parameter comprises a voltage threshold level.
 23. The method according to claim 21 wherein said at least one detection sensitivity parameter comprises at least one morphological detection parameter.
 24. The method according to claim 21 wherein said set of data is a degenerate set of data in which at least some of said sets of alert time window parameters of said plurality of sets of alert time window parameters have identical values of said at least one detection sensitivity parameter.
 25. The method according to claim 20 wherein said plurality of cardiac condition defining parameters comprises a cycle length category parameter, said cycle length category parameter has a value selected from a plurality of preset values each one of said plurality of preset values represents a different range of beat cycle lengths, one of said plurality of cardiac condition defining variables is a cycle length category variable, and wherein said step of updating includes updating the value of said cycle length category variable by determining the cycle length range into which the current measured beat to beat time interval falls and by setting as the value of said cycle length category variable one of said plurality of preset values corresponding with said cycle length range.
 26. The method according to claim 20 wherein said plurality of cardiac conditions comprises beats initiated by the natural pacemaker of said heart and beats initiated by a pacing pulse delivered by said excitable tissue control device, one of said plurality of cardiac condition defining parameters is a parameter which may have a first value defining beats initiated by the natural pacemaker of said heart or a second value defining beats initiated by a pacing pulse delivered by said excitable tissue control device, and wherein one of said plurality of cardiac condition defining variables is a variable which may have the said first value defining a current beat initiated by the natural pacemaker of said heart or the said second value defining a current beat initiated by a pacing pulse delivered by said excitable tissue control device.
 27. The method according to claim 20 wherein said plurality of cardiac conditions further comprises beats occurring during a time period in which the prior application of excitable tissue control signals results in a change of the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart, and beats occurring during a time period in which the prior application of excitable tissue control signals does not result in a change in the velocity of propagation of a depolarization wave in said portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart.
 28. The method according to claim 20 wherein said set of timing parameters of said alert time window parameters comprises a beginning time point value and an ending time point value for an alert time window.
 29. The method according to claim 20 wherein said excitable tissue control device is provided with a value of the bin duration of a time bin used for collecting data within said data collection session, said set of timing parameters of said alert time window parameters comprises a starting bin number and an ending bin number and wherein said step of using includes computing the starting time point and ending time point of said alert time window from said bin duration, said starting bin number and said ending bin number prior to said starting of said alert time window.
 30. The method according to claim 20 wherein said set of timing parameters comprises a set of approximation parameters and wherein said processing of said step of providing comprises using an approximation method to process said data collected from said heart in said data collection session to obtain a plurality of sets of approximation parameters, usable for computing improved approximated values of the beginning time point and the ending time point of said alert time window.
 31. The method according to claim 30 wherein said approximation method is a linear piecewise approximation method, said set of approximation parameters comprises a beginning time point parameter and a first slope parameter associated with said beginning time point parameter, an ending time point parameter and a second slope parameter associated with said ending time point parameter, and wherein said step of using comprises computing an approximated beginning time point for said alert time window of said current beat cycle from the values of the current cycle length, said first slope parameter and said beginning time point parameter, and computing an approximated ending time point for said alert time window of said current beat cycle from the values of said current cycle length, said second slope parameter and said ending time point parameter.
 32. The method according to claim 31 wherein said current cycle length is the instantaneous cycle length determined from the current R—R interval or the current A—A interval measured for said current beat cycle.
 33. The method according to claim 31 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive R—R intervals including the R—R interval of said current beat cycle.
 34. The method according to claim 31 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive A—A intervals including the A—A interval of said current beat cycle.
 35. The method according to claim 20 wherein said set of timing parameters comprises said beginning time point and said ending time point of said alert time window.
 36. The method according to claim 20 wherein said set of data is a degenerate set of data in which the values of said set of timing parameters of at least some of the sets of said plurality of sets of alert time window parameters are identical.
 37. The method according to claim 20 wherein said first cardiac site is the right ventricle of said heart and said second cardiac site is the left ventricle of said heart.
 38. The method according to claim 20 wherein said first cardiac site is the right atrium of said heart and said second cardiac site is the left ventricle of said heart.
 39. An excitable tissue control device for setting on a beat by beat basis the parameters of an alert time window under a plurality of different cardiac conditions of a heart of a patient, the device comprising: a plurality of electrodes adapted to be implanted in or about said heart; detection circuitry for detecting electrical depolarization events in a first cardiac site through at least a first electrode of said plurality of electrodes, said at least first electrode is disposed in or about said first cardiac site, and for detecting electrical depolarization events in a second cardiac site through at least a second electrode of said plurality of electrodes, said at least second electrode is disposed in or about said second cardiac site; an excitable tissue control unit for delivering non-excitatory excitable tissue control signals to at least part of said second cardiac site through one or more electrodes of said plurality of electrodes; a memory unit for storing a set of data, said set of data comprises a plurality of sets of alert time window parameters, each set of alert time window parameters is uniquely associated with a different set of values of a plurality of cardiac condition defining parameters identifying one of said plurality of different cardiac conditions, each set of alert time window parameters comprises at least a set of timing parameters usable for obtaining a beginning time point and an ending time point for said alert time window, each set of alert time window parameters is obtained by processing data collected from a plurality of cardiac beats of said heart of said patient under said plurality of different cardiac conditions within a data collection session performed in said patient; a processor unit operatively connected to said detection circuitry, said excitable tissue control unit and said memory unit, for receiving detection signals from said detection circuitry, for controlling said excitable tissue control unit by using the received detection signals, for updating in a current beat cycle of said heart the values of a plurality of cardiac condition defining variables corresponding to said cardiac condition defining parameters, for automatically selecting for said current beat cycle a current set of alert time window parameters of said plurality of sets of alert time window parameters based on the current values of said cardiac condition defining variables, for applying said current set of alert time window parameters to start said alert time window within said current beat cycle after detecting a first depolarization event at or about said first cardiac site and to terminate said alert time window, and for initiating the delivery of a delayed excitable tissue control signal at or about said second cardiac site upon detecting within the duration of said alert time window a depolarization event in or about said second cardiac site of said heart; and a power source for providing power to said detection circuitry, said processor unit said memory unit and said excitable tissue control unit.
 40. The device according to claim 39 further including a telemetry unit operatively connected to said power source and said processor unit for telemetrically receiving data from a second telemetry unit disposed outside said patient.
 41. The device according to claim 39 wherein said plurality of sets of alert time window parameters of said set of data are stored in said memory unit as a data array or a look up table.
 42. The device according to claim 39 wherein said detection circuitry is adapted for being controllably switched between a plurality of detection sensitivity levels, and wherein each set of alert time window parameters of said plurality of sets of alert time window parameters further comprises at least one detection sensitivity parameter having a value representing one of said plurality of detection sensitivity levels of said detection circuitry, and wherein said processor unit is adapted for using said value of said at least one detection sensitivity parameter of said current beat cycle to switch said detection circuitry to a detection sensitivity level represented by said at least one detection sensitivity parameter of said current beat cycle.
 43. The device according to claim 42 wherein said detection circuitry is adapted for being switched between a plurality of voltage threshold levels and said at least one detection sensitivity parameter comprises a voltage threshold level.
 44. The device according to claim 42 wherein said detection circuitry is adapted for performing event detection based on a morphological detection method and wherein said at least one detection sensitivity parameter comprises at least one morphological detection parameter.
 45. The device according to claim 40 wherein said set of data is a degenerate set of data in which at least some of said sets of alert time window parameters of said plurality of sets of alert time window parameters have identical values of said at least one detection sensitivity parameter.
 46. The device according to claim 39 wherein said plurality of cardiac conditions comprises beats having a plurality of different beat to beat time intervals representing different instantaneous heart rates of said heart.
 47. The device according to claim 46 wherein said plurality of cardiac conditions further comprises beats occurring during a time period in which the prior application of excitable tissue control signals results in a change of the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart, and beats occurring during a time period in which the prior application of excitable tissue control signals does not result in a change in the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart.
 48. The device according to claim 39 wherein said plurality of cardiac conditions comprises beats occurring during a time period in which the prior application of excitable tissue control signals results in a change of the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart, and beats occurring during a time period in which the prior application of excitable tissue control signals does not result in a change in the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart.
 49. The device according to claim 39 further including a pacing unit operatively connected to said power source, said processor unit and to at least one electrode of said plurality of electrodes for delivering pacing pulses to said heart through said at least one electrode.
 50. The device according to claim 49 wherein said plurality of cardiac conditions comprises beats initiated by the natural pacemaker of said heart and beats initiated by a pacing pulse delivered by said excitable tissue control device.
 51. The device according to claim 50 wherein said plurality of cardiac conditions further comprise beats having a plurality of different beat to beat time intervals representing different instantaneous heart rates of said heart.
 52. The device according to claim 51 wherein said plurality of cardiac conditions further comprises beats occurring during a time period in which the prior application of excitable tissue control signals results in a change of the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart, and beats occurring during a time period in which the prior application of excitable tissue control signals does not result in a change in the velocity of propagation of a depolarization wave in at least a portion of the myocardial tissue disposed between said first cardiac site and said second cardiac site of said heart.
 53. The device according to claim 39 wherein said set of timing parameters of said alert time window parameters comprises a beginning time point value and an ending time point value for said alert time window.
 54. The device according to claim 39 wherein said excitable tissue control device is provided with a value of the bin duration of a time bin used for collecting data within said data collection session, said value is stored in said memory unit, wherein said set of timing parameters of said alert time window parameters comprises a starting bin number and an ending bin number and wherein said processor unit is adapted for computing the starting time point and ending time point of said alert time window from said bin duration, said starting bin number and said ending bin number, prior to starting of said alert time window within said current beat cycle.
 55. The device according to claim 39 wherein said set of timing parameters comprises a set of approximation parameters and wherein said processing comprises using an approximation method to process said data collected from said heart in said data collection session to obtain a plurality of sets of approximation parameters usable for computing improved approximated values of the beginning time point and the ending time point of said alert time window.
 56. The device according to claim 55 wherein said approximation method is a linear piecewise approximation method, said set of approximation parameters comprises a beginning time point parameter and a first slope parameter associated with said beginning time point parameter, an ending time point parameter and a second slope parameter associated with said ending time point parameter, and wherein said step of using comprises computing an approximated beginning time point for said alert time window of said current beat cycle from the values of the current cycle length measured for said current beat cycle, said first slope parameter and said beginning time point parameter, and computing an approximated ending time point for said alert time window of said current beat cycle from the values of said current cycle length, said second slope parameter and said ending time point parameter.
 57. The device according to claim 56 wherein said current cycle length is the instantaneous cycle length determined from the current R—R interval or the current A—A interval measured for said current beat cycle.
 58. The device according to claim 56 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive R—R intervals including the R—R interval of said current beat cycle.
 59. The device according to claim 50 wherein said current cycle length is an average cycle length computed from the values of a plurality of consecutive A—A intervals including the A—A interval of said current beat cycle.
 60. The device according to claim 39 wherein said set of timing parameters comprises said beginning time point and said ending time point of said alert time window.
 61. The device according to claim 39 wherein said set of data is a degenerate set of data in which at least some of said sets of alert time window parameters of said plurality of sets of alert time window parameters have identical values of said set of timing parameters.
 62. The device according to claim 39 wherein said first cardiac site is the right ventricle of said heart and said second cardiac site is the left ventricle of said heart.
 63. The device according to claim 39 wherein said first cardiac site is the right atrium of said heart and said second cardiac site is the left ventricle of said heart.
 64. The device according to claim 39 wherein said excitable tissue control device is adapted to be implanted in said patient.
 65. The device according to claim 39 wherein said excitable tissue control device is disposed out of said patient and is operatively connected to said plurality of electrodes adapted to be implanted in or about said heart of said patient.
 66. An excitable tissue control device for setting on a beat by beat basis the parameters of an alert time window under a plurality of different cardiac conditions of a heart of a patient, the device comprising: a plurality of electrodes adapted to be implanted in or about said heart; means for detecting electrical depolarization events in a first cardiac site through at least a first electrode of said plurality of electrodes, said at least first electrode is disposed in or about said first cardiac site, and for detecting electrical depolarization events in a second cardiac site through at least a second electrode of said plurality of electrodes, said at least second electrode is disposed in or about said second cardiac site; excitable tissue control means for delivering non-excitatory excitable tissue control signals to at least part of said second cardiac site through one or more electrodes of said plurality of electrodes; memory means for storing a set of data, said set of data comprises a plurality of sets of alert time window parameters, each set of alert time window parameters is uniquely associated with a different set of values of a plurality of cardiac condition defining parameters identifying one of said plurality of different cardiac conditions, each set of alert time window parameters comprises at least a set of timing parameters usable for obtaining a beginning time point and an ending time point for said alert time window, each set of alert time window parameters is obtained by processing data collected from a plurality of cardiac beats of said heart of said patient under said plurality of different cardiac conditions within a data collection session performed in said patient; processing means operatively connected to said detection means, said excitable tissue control means and said memory means, for receiving detection signals from said detection means, for controlling said excitable tissue control means by using the received detection signals, for updating in a current beat cycle of said heart the values of a plurality of cardiac condition defining variables corresponding to said cardiac condition defining parameters, for automatically selecting for said current beat cycle a current set of alert time window parameters of said plurality of sets of alert time window parameters based on the current values of said cardiac condition defining variables, for applying said current set of alert time window parameters to start said alert time window within said current beat cycle after detecting a first depolarization event at or about said first cardiac site and to terminate said alert time window, and for initiating the delivery of a delayed excitable tissue control signal at or about said second cardiac site upon detecting within the duration of said alert time window a depolarization event in or about said second cardiac site of said heart; and a power source for providing power to said detection means, said processing means said memory means and said excitable tissue control means.
 67. The device according to claim 66 further including telemetry means operatively connected to said power source and said processing means for telemetrically receiving data from a second telemetry means disposed outside said patient.
 68. The device according to claim 66 further including pacing means operatively connected to said power source, said processing means and to at least one electrode of said plurality of electrodes, for delivering pacing pulses to said heart through said at least one electrode. 